A Study of MDI-1228_mesylate Ophthalmic Solution in Healthy Adults and Participants With Allergic Conjunctivitis
Study Details
Study Description
Brief Summary
The goal of this clinical trial is to evaluate the safety, tolerability and pharmacokinetics (PK) profiles* of MDI-1228_mesylate Ophthalmic Solution in patients with allergic conjunctivitis and healthy adult participants. This trial also aims to study the preliminary efficacy of MDI-1228_mesylate Ophthalmic Solution in patients with allergic conjunctivitis.
Participants will receive either of the following treatment:
-
MDI-1228_mesylate Ophthalmic Solution, or
-
Placebo**
Researchers will observe any changes in heath (if any) in participants receiving the study treatment to evaluate the safety of study drug. Researchers will also focus on any changes in symptoms of patients with allergic conjunctivitis to evaluate the efficacy of study drug.
Note:
*PK profiles: how the drug interacts with the body.
**placebo: a harmless substance that contains no active agents.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Experimental group Including single dose groups at 2 dose levels (0.1% and 0.3%) and multiple-dose groups at 2 dose levels (0.1% and 0.3%): In Part A, 8 (80%) healthy participants in cohort 1a will receive a single dose of 0.1% MDI-1228_mesylate Ophthalmic Solution; 8 (80%) healthy participants in cohort 2a will receive a single dose 0.3% MDI-1228_mesylate Ophthalmic Solution. In Part B, 8 (80%) participants with allergic conjunctivitis in cohort 1b will receive 0.1% MDI-1228_mesylate Ophthalmic Solution twice daily on Days 1 to 6 and a single dose in the morning of Day 7; 8 (80%) participants with allergic conjunctivitis in cohort 2b will receive 0.3% MDI-1228_mesylate Ophthalmic Solution twice daily on Days 1 to 6 and a single dose in the morning of Day 7. |
Drug: MDI-1228_mesylate Ophthalmic Solution
MDI-1228_mesylate Ophthalmic Solution includes 2 strengths:
0.1% (0.4 mL [0.4 mg] free base)
0.3% (0.4 mL [1.2 mg] free base)
For each dose, MDI-1228_mesylate Ophthalmic Solution is administered by clinical research unit staff via conjunctival instillation with 2 drops to the right eye (ie, study eye). In Part B of the study, the participants will receive 12 ±1 hours between doses. The manufacturing site for MDI-1228_mesylate Ophthalmic Solution of the clinical supply materials was Tianjin Kingyork Hebei Univision Pharmaceutical Co., Ltd.
|
| Placebo Comparator: Comparator group In Part A, 2 (20%) healthy participants in cohort 1a will receive a single dose of placebo as comparator of 0.1% MDI-1228_mesylate Ophthalmic Solution; 2 (20%) healthy participants in cohort 2a will receive a single dose of placebo as comparator of 0.3% MDI-1228_mesylate Ophthalmic Solution. In Part B, 2 (20%) participants with allergic conjunctivitis in cohort 1b will receive placebo twice daily on Days 1 to 6 and a single dose in the morning of Day 7 as comparator of 0.1% MDI-1228_mesylate Ophthalmic Solution; 2 (20%) participants with allergic conjunctivitis in cohort 2b will receive placebo twice daily on Days 1 to 6 and a single dose in the morning of Day 7 as comparator of 0.3% MDI-1228_mesylate Ophthalmic Solution. |
Drug: Placebo
The components employed in the placebo formulation are the same as those used for the active formulation except MDI-1228_mesylate is absent.
For each dose, the placebo is administered via conjunctival instillation with 2 drops to the right eye (ie, study eye).
The manufacturing site for placebo of the clinical supply materials was Tianjin Kingyork Hebei Univision Pharmaceutical Co., Ltd.
|
Outcome Measures
Primary Outcome Measures
- Part A and B - Incidence and severity of all systemic or ocular treatment emergent adverse events (TEAEs) [From first dose to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Systemic or ocular TEAEs will be collected from spontaneous reports and direct observation. The investigator will make an assessment of intensity for each TEAE and assign it to one of the Common Terminology Criteria for Adverse Events (CTCAE) categories: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), and grade 5 (death).
- Part A and B - Assessment of vital sign measurement results - respiratory rate [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Respiratory rate (breaths/minute) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.
- Part A and B - Assessment of vital sign measurement results - heart rate [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Heart rate (beats/minute) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.
- Part A and B - Assessment of vital sign measurement results - blood pressure [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Blood pressure (mmHg) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.
- Part A and B - Assessment of vital sign measurement results - body temperature [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Body temperature (℃) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.
- Part A and B - Assessment of physical examination results - general appearance [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Assessment of general appearance (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of physical examination results - head, eyes, ears, nose, and throat (HEENT) [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Assessment of HEENT (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of physical examination results - neck (including thyroid and nodes) [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Assessment of neck (including thyroid and nodes) (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of physical examination results - cardiovascular system [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Assessment of cardiovascular system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of physical examination results - respiratory system [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Assessment of respiratory system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of physical examination results - gastrointestinal system [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Assessment of gastrointestinal system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of physical examination results - renal system [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Assessment of renal system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of physical examination results - neurological system [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Assessment of neurological system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of physical examination results - musculoskeletal system [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Assessment of musculoskeletal system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of physical examination results - skin [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Assessment of skin (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of 12-lead electrocardiogram (ECG) results - heart rate [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in heart rate (beats/min) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate (repeat for 3 times), with 1- to 2-minute intervals between ECG readings.
- Part A and B - Assessment of 12-lead ECG results - PR interval [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in PR interval (milliseconds) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.
- Part A and B - Assessment of 12-lead ECG results - QRS complex [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in QRS complex as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.
- Part A and B - Assessment of 12-lead ECG results - QT interval corrected with Fridericia Formula (QTcF) [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in QTcF (milliseconds) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.
- Part A and B - Assessment of 12-lead ECG results - RR interval [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in RR interval (milliseconds) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.
- Part A and B - Ophthalmic assessment - corrected visual acuity (CVA) [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
CVA (6/6 or 20/20 system) will be assessed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
- Part A and B - Ophthalmic assessment - best corrected visual acuity (BCVA) (for subjects with CVA below 6/6 or 20/20 only) [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
BCVA examination is required to confirm whether the subject's best-corrected visual acuity is reduced in subjects with visual acuity below 6/6 or 20/20 during the follow-up after the screening period.
- Part A and B - Ophthalmic assessment - intraocular pressure [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Intraocular pressure (mmHg) will be assessed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
- Part A and B - Ophthalmic assessment - light response pupil test [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Light response pupil test (positive/negative) will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
- Part A and B - Ophthalmic assessment - extraocular movement test [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Extraocular movement test will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
- Part A and B - Ophthalmic assessment - visual field test [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Visual field test will be performed at screening, Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
- Part A and B - Ophthalmic assessment - slit-lamp examination [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Slit-lamp examination will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
- Part A and B - Ophthalmic assessment - corneal fluorescein staining test [From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)]
Corneal fluorescein staining test will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
- Part A and B - Ophthalmic assessment - dilated fundus examination [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Dilated fundus examination will be performed at screening, Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
- Part A and B - Ophthalmic assessment - optical coherence tomography (OCT) eye examination [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
OCT eye examination will be performed at screening, Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
- Part A and B - Assessment of hematology results - hemoglobin [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in hemoglobin (g/dL) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of hematology results - hematocrit [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in hematocrit (%) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of hematology results - red blood cell count [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in red blood cell count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of hematology results - white blood cell count [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in white blood cell count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of hematology results - neutrophil count [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in neutrophil count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of hematology results - lymphocyte count [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in lymphocyte count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of hematology results - monocyte count [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in monocyte count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of hematology results - basophil count [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in basophil count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of hematology results - eosinophil count [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in eosinophil count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of hematology results - platelet count [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in platelet count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of coagulation results - international normalized ratio (INR) [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
A coagulation test will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in INR from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of coagulation results - activated partial thromboplastin time (aPTT) [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
A coagulation test will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in aPTT (seconds) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of coagulation results - prothrombin time (PT) [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
A coagulation test will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in PT (seconds) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - sodium [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood sodium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - potassium [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood potassium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - chloride [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood chloride (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - calcium [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood calcium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - bicarbonate [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline in blood bicarbonate (mmol/L) and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - albumin [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline in blood albumin (g/dL) and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - total protein [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in total protein (g/dL) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - creatinine [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood creatinine (μmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - estimated glomerular filtration rate (GFR) [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline in estimated GFR (mL/min) and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - urea [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood urea (μmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - aspartate aminotransferase (AST) [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in AST (units/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - alanine aminotransferase (ALT) [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in ALT (units/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - gamma glutamyl transpeptidase (GGT) [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in GGT (units/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - alkaline phosphatase (ALP) [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in ALP (units/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - phosphorous [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood phosphorous (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - total bilirubin (direct and indirect) [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in total bilirubin (μmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - amylase [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood amylase (units/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - cholesterol [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in cholesterol (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - triglycerides [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in triglycerides (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - uric acid [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in uric acid (μmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - creatine phosphokinase [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in creatine phosphokinase (units/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - lactate dehydrogenase [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in lactate dehydrogenase (units/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - magnesium [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood magnesium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - fasting glucose [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in fasting glucose (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - anion gap [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in anion gap (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - adjusted calcium [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in adjusted calcium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - globulin [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in globulin (g/dL) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of blood biochemistry results - ionized calcium [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in ionized calcium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of urinalysis results - pH [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in pH from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of urinalysis results - specific gravity [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in specific gravity from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of urinalysis results - urine glucose [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine glucose (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of urinalysis results - urine protein [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine protein (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of urinalysis results - urine ketones [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine ketones (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of urinalysis results - urine blood [From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)]
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine blood (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.
- Part A and B - Assessment of scores of conjunctival hyperemia [From pre-dose to post-dose (Day 2 in Part A, Day 8 in Part B)]
Scores of conjunctival hyperemia (0 to 4 scores, a higher score indicates a more severe condition) will be assessed to record the change from the pre-dose (Day -1) scores to the post-dose scores (Day 2 for Part A, Day 8 for Part B) in the study eye.
- Part A and B - Assessment of scores of corneal staining [From pre-dose to post-dose (Day 2 in Part A, Day 8 in Part B)]
Scores of corneal staining (0 to 4 scores, a higher score indicates a more severe condition) will be assessed to record the change from the pre-dose (Day -1) scores to the post-dose scores (Day 2 for Part A, Day 8 for Part B) in the study eye.
Secondary Outcome Measures
- Part A - Maximum concentration (Cmax) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 7±1 day)]
Cmax means the highest concentration a drug reaches in the plasma after administration. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
- Part A and B - Time to maximum concentration (Tmax) of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 7±1 day in Part A, Day 14±1 day in Part B)]
Tmax refers to the time a drug takes to reach the highest concentration in the plasma after administration. It will be measured after the subject receives a single dose (Part A) or multiple doses (Part B) of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
- Part A and B - Half-life (T1/2) of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 7±1 day in Part A, Day 14±1 day in Part B)]
T1/2 refers to the time a drug takes to be eliminated to half of the highest concentration in the plasma after administration. It will be measured after the subject receives a single dose (Part A) or multiple doses (Part B) of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
- Part A - Systemic clearance (CL or CL/F) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 7±1 day)]
Systemic CL refers to the total volume of fluid cleared of drug from the body per unit of time, usually expressed in mL/min. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
- Part A - Volume of distribution (Vd) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 7±1 day)]
Vd refers to fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
- Part A - Mean retention time (MRT) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 7±1 day)]
MRT reflects the average time a drug molecule spends in the body. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
- Part A - Area under curve until time t (AUC0-t) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 7±1 day)]
AUC0-t refers to area under the plasma concentration-time curve until time t and reflects the actual body exposure to drug after administration at time t. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
- Part A - Area under curve until infinity (AUC0-∞) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 7±1 day)]
AUC0-∞ refers to area under the plasma concentration-time curve until infinity and reflects the total body exposure to drug. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
- Part B - Trough concentration at steady state (Css_min) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 14±1 day)]
Css_min means the lowest concentration of drug in the blood within a steady-state dosing interval. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
- Part B - Maximum plasma concentration at steady state (Css_max) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 14±1 day)]
Css_max means the highest concentration of drug in the blood observed after intermittent dosage administration. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
- Part B - Average plasma concentration at steady state (Css_av) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 14±1 day)]
Css_av means the average drug concentration reached during a steady-state intermittent dosing interval. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
- Part B - Clearance (CL or CL/F) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 14±1 day)]
CL means the volume of fluid cleared of drug from the body per unit of time, usually expressed in mL/min. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
- Part B - Area under the plasma concentration-time curve at steady state (AUCss) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 14±1 day)]
AUCss reflects the exposure of drug in the body at steady state. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
- Part B - Coefficient of fluctuation (DF) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution [Post-first dose on Day 1 to EOS (Day 14±1 day)]
DF reflects difference between the highest and lowest concentration of drug in the body at steady state. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
- Part B - Assessment of scores in the study and fellow eye of eye itching [Post-first dose on Day 1 to end of treatment (Day 7)]
Preliminarily efficacy after multiple doses of MDI-1228_mesylate Ophthalmic Solution in participants with allergic conjunctivitis will be evaluated using the conjunctival allergen challenge (CAC) Model. Changes in scores in the study and fellow eye of eye itching (0 to 4 scores, a higher score indicates a more severe condition) between the following timepoints will be assessed: post-first dose on Day 1 compared to the pre- dose scores at baseline post-CAC (3, 5 and 7 minutes [±1 minute]) post-dose on Day 7 compared to the pre-dose scores at baseline post-CAC (3, 5 and 7 minutes [±1 minute])
- Part B - Assessment of scores in the study and fellow eye of eye redness [Post-first dose on Day 1 to end of treatment (Day 7)]
Preliminarily efficacy after multiple doses of MDI-1228_mesylate Ophthalmic Solution in participants with allergic conjunctivitis will be performed using the conjunctival allergen challenge (CAC) Model. Changes in scores in the study and fellow eye of eye redness (0 to 3 scores, a higher score indicates a more severe condition) between the following time points will be assessed: post-first dose on Day 1 compared to the pre- dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]). post-dose on Day 7 compared to the pre-dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]).
- Part B - Assessment of scores in the study and fellow eye of tearing [Post-first dose on Day 1 to end of treatment (Day 7)]
Preliminarily efficacy after multiple doses of MDI-1228_mesylate Ophthalmic Solution in participants with allergic conjunctivitis will be performed using the conjunctival allergen challenge (CAC) Model. Changes in scores in the study and fellow eye of tearing (0 to 3 scores, a higher score indicates a more severe condition) between the following time points will be assessed: post-first dose on Day 1 compared to the pre- dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]). post-dose on Day 7 compared to the pre-dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]).
- Part B - Assessment of scores in the study and fellow eye of chemosis [Post-first dose on Day 1 to end of treatment (Day 7)]
Preliminarily efficacy after multiple doses of MDI-1228_mesylate Ophthalmic Solution in participants with allergic conjunctivitis will be performed using the conjunctival allergen challenge (CAC) Model. Changes in scores in the study and fellow eye of chemosis (0 to 3 scores, a higher score indicates a more severe condition) between the following time points will be assessed: post-first dose on Day 1 compared to the pre- dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]). post-dose on Day 7 compared to the pre-dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Weight ≥ 50 kg for males, ≥ 45 kg for females, with the BMI (BMI = weight[kg]/height[m]2) between 18 and 32 (inclusive)
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The corrected visual acuity (CVA) of both eyes should be 6/6 or 20/20 (Snellen chart), with an intraocular pressure between 10 and 21 mmHg (inclusive) and a difference in intraocular pressure between the 2 eyes < 5 mmHg.
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Normal vital signs after ≥ 5 minutes resting supine or semi supine position:
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≥ 90 mmHg and ≤160 mmHg (systolic blood pressure)
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≥50 mmHg and ≤ 95 mmHg (diastolic blood pressure)
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≥ 45 beats per minute (bpm) and ≤ 100 bpm (heart rate)
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Body temperature >35.5℃ and ≤37.7℃
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Standard 12-lead ECG parameters after ≥5 minutes resting in supine or semi-supine position with PR > 120 ms and < 220 ms, QRS < 120 ms, QTcF ≤ 450 ms for males and ≤ 470 ms for females, and otherwise normal ECG (all data limits are based on average readings of the ECGs).
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Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or use highly effective contraceptive method as assessed by the PI (OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring or an IUD) from screening until study completion, including the follow up period for at least 30 days after the last dose of study drug, or be post-menopausal for ≥ 12 months. Post-menopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels at screening for amenorrheic female participants. Females who are abstinent from heterosexual intercourse as part of their usual lifestyle will also be eligible for participation.
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Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and admission and be willing to have additional pregnancy tests as required throughout the study.
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Males must be surgically sterile (> 30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method as assessed by the PI from screening until study completion, including the follow up period, for at least 30 days after the last dose of study drug. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner (WOCBP) that includes: OCPs, long- acting implantable hormones, injectable hormones, a vaginal ring, or an IUD. Male participants whose female partner is post-menopausal, and participants who are abstinent from heterosexual intercourse as part of their usual lifestyle and are not planning to conceive will also be eligible.
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Male participants must agree to refrain from donating sperm and female participants from donating ova from screening until study completion, including the follow up period, for at least 90 days after the last dose of study drug.
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Provides written informed consent and is willing and able to undergo all study procedures and attend the scheduled follow up visit/s per protocol.
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Are willing to consume clinical research unit (CRU) provided standard meals.
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Have no neck or back issues which prevents the participant having their head tilted back for dosing at the discretion of the Investigator.
For Part A: Single Ascending Dose in Healthy Volunteers
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Males and females aged 18 to 55 years old (inclusive)
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Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, safety laboratory tests, and ECG. A potential participant with a clinical abnormality or laboratory parameters outside the normal reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. The Investigator may discuss with the local MM and Sponsor MM as required.
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Have no abnormal results or abnormal not clinically significant (as determined by the Investigator) results of ocular examinations of both eyes (including slit-lamp examination, corneal fluorescein staining test, light response pupil test, extraocular movement test, visual field test, posterior OCT eye examination, dilated fundus examination)
For Part B: Multiple Ascending Doses in Participants with Allergic Conjunctivitis
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Male and female participants aged 18 to 65 years (inclusive)
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Positive conjunctival allergen challenge (CAC) for both eyes at screening. During the screening period CAC tests that are positive for the first test will be confirmed by a second test at least 7 days later.
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Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, safety laboratory tests, vital signs, and ECG, with the exception of abnormal clinically significant results related to allergic conjunctivitis.
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A potential participant with a clinical abnormality or laboratory parameters outside the normal reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. The Investigator may discuss with the local medical monitor (MM) and Sponsor MM as required.
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Have no abnormal results or have abnormal but not clinically significant (as determined by the investigator) results of ocular examinations of both eyes (including slit-lamp examination, corneal fluorescein staining test, light response pupil test, extraocular movement test, visual field test, posterior optical coherence tomography (OCT) eye examination, dilated fundus examination), except for abnormal signs caused by allergic conjunctivitis (AC) (such as: conjunctival hyperemia, edema, and papillary hypertrophy conjunctiva).
Exclusion Criteria:
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Have a current or past history of clinically significant eye disorder (allergic conjunctivitis condition is not applicable for Part B), circulatory system diseases, respiratory disorders, hepatobiliary disorders, digestive disorders, urinary system diseases, renal disorders, endocrine disorders, immune system disorders, malignancies, metabolic disorders, mental disorders, or nervous system diseases that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk to the participant by virtue of their participation in the study. Participant with a history of uncomplicated kidney stones (defined as spontaneous passage and no recurrence in the last 5 years); uncomplicated cholecystectomy; Gilbert's syndrome; a past history of being treated by non-current depression may be enrolled in the study at the discretion of the Investigator. Participants with a history of childhood asthma (without hospitalization) that has symptomatically resolved and remains untreated may participant.
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Have healed eye disorders (such as infection, trauma) in either eye within 1 month prior to the first dose.
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Have a history of intraocular surgery and laser eye surgery in either eye.
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Used any ocular products (including various eye drops or eye gel) within 14 days or 5 half-lives (whichever is longer) prior to screening.
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Wore contact lenses within 7 days prior to baseline or need to wear contact lenses throughout the clinical study.
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Current evidence or history of COVID-19 or influenza-like illness as defined by fever (> 37.7°C) and 2 or more of the following symptoms within 7 days before dosing: cough, sore throat, runny nose, sneezing, limb/joint pain, headache, vomiting/diarrhea in the absence of a known cause, other than influenza or COVID-19 infection.
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A history of Hepatitis B, Hepatitis C, or HIV infection and/or a positive pre-study HIV, Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
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Participants who are intolerant of venipuncture blood collection or have poor venous access and/or have a history of fear of needles and hemophobia.
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Used Janus kinase (JAK) inhibitors or immunosuppressants or any other prescription drugs, traditional Chinese medicines or Chinese patent medicines within 4 weeks prior to Day -1; or used over-the-counter (OTC) drugs or health products within 2 weeks prior to Day -1, unless with a washout period of more than 5 half-lives for products with a longer half-life.
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Was vaccinated within 2 weeks prior to screening or plan to be vaccinated during the study.
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Had major surgery within 6 months prior to screening or plan to undergo surgery during the study.
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Participants who smoked more than 5 cigarettes/pipes/vaping per day on average or excessive use of any nicotine product (> 5 products on average per day) within 3 months prior to screening and not able to abstain from smoking from screening to end of study (EoS).
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Any other serious medical condition or abnormality that, in the Investigator's judgment, precludes the participant's safe participation in and completion of the study.
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A positive pre-study drug or alcohol screen. A positive drug or alcohol screen test result may be verified by re-testing (up to 1 false positive result permitted) and may be followed up at the discretion of the Investigator.
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History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of > 21 units for males or > 14 units for females. One unit is equivalent to 10 g of alcohol and the following can be used as a guide: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (30 mL) measure of spirits.
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The participant is unwilling to abstain from alcohol consumption from 24 hours prior to dosing until discharge from the CRU, and for 24 hours prior to all other outpatient visits to the CRU.
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Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human or humanized antibodies, fusion proteins, MDI-1228_mesylate Ophthalmic Solution excipients, any material used for assessments (e.g., fluorescein, tropicamide, etc), or a history of drug or other allergy including severe allergic reaction that in the opinion of the Investigator contraindicates their participation.
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Participation in a clinical trial within 30 days before randomization; use of any experimental therapy within 30 days or 5 half-lives prior to randomization, whichever is greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to randomization, whichever is greater.
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Pregnant or breastfeeding WOCBP.
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Donation within the last 3 months of > 499 mL whole blood or within 2 weeks of any volume of plasma.
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Participant unable to provide written informed consent or participant under guardianship.
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Unwilling or unable to follow protocol requirements, including attendance at follow up visit/s.
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Any history of severe ocular trauma in either eye at any time.
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Any history of previous intraocular or ocular laser surgery or any refractive surgery procedure within the past 6 months of the screening visit in either eye;
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Current or chronic history of clinically significant ocular disease within the past 3 months of screening visit in either eye.
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Current or chronic history of ocular infection (bacterial, viral, or fungal) or corneal irritation within the past 3 months of screening visit in either eye.
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Abnormal tearing, OR expected regular use of prescription or expected use of OTC tear substitutes within 4 weeks prior to Day -1, and for the duration of the study.
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Previous or expected use of ocular (topical, periocular, intravitreal), local (inhaled or nasal), or systemic steroid or glucocorticoid medications within 4 weeks prior to Day -1, and for the duration of the study.
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At the ophthalmic Investigator's discretion, any participants who have a history of any significant ocular conditions in either eye that would contraindicate the use of the study medication, or that might affect the study conduct, or the interpretation of the study results.
For Part A: Single Ascending Dose in Healthy Volunteers
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Clinically significant findings as determined by the Investigator in other ocular examinations (e.g., conjunctival hyperemia grade >1, corneal fluorescein staining score ≥ 2, or other chronic or acute eye disorders).
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History of or presence of Inflammatory ocular disease (iritis, uveitis, herpetic keratitis, AC).
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Presence of an ocular pathology such as blepharitis, conjunctivitis, uveitis, or any other ocular infection or inflammation.
For Part B: Multiple Ascending Doses in Participants with Allergic Conjunctivitis
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Clinically significant findings in other ocular examinations, except for abnormal signs caused by AC (such as: conjunctival hyperemia, edema, and papillary hypertrophy conjunctiva).
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Inflammation or infectious disease of the anterior segment other than AC in either eye.
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Be willing and able to stop current treatment (topical and systemic) for conjunctival allergy for the study duration.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CMAX Clinical Research | Adelaide | South Australia | Australia | 5000 |
Sponsors and Collaborators
- Shanghai Medinno Pharmaceutical Technology Co., Ltd.
Investigators
- Principal Investigator: Sepehr Shakib, PhD, CMAX Clinical Research
- Study Director: Liang Lu, PhD, Shanghai Medinno Pharmaceutical Technology Co., Ltd.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MDI-1228-I-AC