Clinical trial NCT05969236: A Study of MDI-1228_mesylate Ophthalmic Solution in Healthy Adults
Official title: A Phase 1, First-in-Human, Single-center, Randomized, Double-masked, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of MDI-1228_mesylate Ophthalmic Solution by Local Instillation in Adult Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Allergic Conjunctivitis
Lead sponsor: Shanghai Medinno Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-08-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This study consists of two parts:

* Part A: Single ascending dose in healthy volunteers
* Part B: Multiple ascending doses in healthy volunteers

The randomization code and the randomization list will be generated using SAS version 9.4 or the latest available version at time of randomization.
Primary purpose: TREATMENT

Brief summary: The main goal of this clinical trial is to evaluate the safety, tolerability and pharmacokinetics (PK) profiles\* of MDI-1228_mesylate Ophthalmic Solution in healthy adult participants.

Participants will receive either of the following treatment:

* MDI-1228_mesylate Ophthalmic Solution, or
* Placebo\*\*

Researchers will observe any changes in health (if any) in participants receiving the study treatment to evaluate the safety and tolerability\*\*\* of the study drug. Researchers will also collect several blood samples from participants to study PK profiles of the drug.

Note:

\*PK profiles: how the drug interacts with the body. \*\*placebo: a harmless substance that contains no active agents. \*\*\*tolerability: how well you can tolerate the drug.


Eligibility criteria: Inclusion Criteria:

1. Weight ≥ 50 kg for males, ≥ 45 kg for females, with the BMI (BMI = weight\[kg\]/height\[m\]2) between 18 and 32 (inclusive) at screening.
2. 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 at screening.
3. Normal vital signs after ≥ 5 minutes resting supine or semi supine position:

   1. ≥ 90 mmHg and ≤160 mmHg (systolic blood pressure)
   2. ≥50 mmHg and ≤ 95 mmHg (diastolic blood pressure)
   3. ≥ 45 beats per minute (bpm) and ≤ 100 bpm (heart rate)
   4. Body temperature ≥35.5℃ and ≤37.7℃
   5. Respiratory Rate≥12 breaths/minute and≤22 breaths/minute
4. Standard 12-lead ECG parameters after ≥5 minutes resting in supine or semi-supine position with PR ≥ 120 ms and ≤ 220 ms, QRSD \< 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) at screening.
5. 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.
6. 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.
7. 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.
8. 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.
9. Provides written informed consent and is willing and able to undergo all study procedures and attend the scheduled follow up visit/s per protocol.
10. Are willing to consume clinical research unit (CRU) provided meals.
11. Have no neck or back issues which prevents the participant having their head tilted back for dosing at the discretion of the Investigator.
12. Males and females aged 18 to 55 years old (inclusive)
13. 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.
14. 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, dilated fundus examination)

Exclusion Criteria:

1. Have a current or past history of clinically significant 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.
2. Have healed eye disorders (such as infection, trauma) in either eye within 1 month prior to the first dose.
3. Have a history of intraocular surgery and laser eye surgery in either eye.
4. Used any ocular products (including various eye drops or eye gel) within 14 days or 5 half-lives (whichever is longer) prior to screening.
5. Wore contact lenses within 2 days prior to baseline (Day -1) or need to wear contact lenses throughout the clinical study.
6. 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.
7. A positive pre-study HIV, Hepatitis B surface antigen or positive Hepatitis C antibody result at screening.
8. Participants who are intolerant of venipuncture blood collection or have poor venous access and/or have a history of fear of needles and hemophobia.
9. 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. The Principal Investigator may review medication on a case-by-case basis to determine if its use would compromise participant safety or interfere with study procedures or data interpretation.
10. Was vaccinated within 2 weeks prior to screening or plan to be vaccinated during the study.
11. Had major surgery within 6 months prior to screening or plan to undergo surgery during the study.
12. 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).
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. Pregnant or breastfeeding WOCBP.
20. Donation within the last 3 months of \> 499 mL whole blood or within 2 weeks of any volume of plasma.
21. Participant unable to provide written informed consent or participant under guardianship.
22. Unwilling or unable to follow protocol requirements, including attendance at follow up visit/s.
23. Any history of severe ocular trauma in either eye at any time.
24. Any history of any refractive surgery procedure within the past 6 months of the screening visit in either eye.
25. Current or chronic history of clinically significant ocular disease within the past 3 months of screening visit in either eye.
26. 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.
27. 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.
28. 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.
29. At the Investigator's or delegate'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.
30. 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).
31. History of clinically significant ocular disease (glaucoma, retinal detachment, iritis, uveitis, herpetic keratitis, etc.) 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.
32. Presence of an ocular pathology such as blepharitis, conjunctivitis, uveitis, or any other ocular infection or inflammation.

Primary outcomes:
measure: Part A and B - Incidence and severity of all systemic or ocular treatment emergent adverse events (TEAEs)
timeFrame: From first dose to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of vital sign measurement results - respiratory rate
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of vital sign measurement results - heart rate
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of vital sign measurement results - blood pressure
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of vital sign measurement results - body temperature
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of physical examination results - general appearance
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of physical examination results - head, eyes, ears, nose, and throat (HEENT)
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of physical examination results - neck (including thyroid and nodes)
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of physical examination results - cardiovascular system
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of physical examination results - respiratory system
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of physical examination results - gastrointestinal system
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of physical examination results - renal system
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of physical examination results - neurological system
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of physical examination results - musculoskeletal system
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of physical examination results - skin
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of 12-lead electrocardiogram (ECG) results - heart rate
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of 12-lead ECG results - PR interval
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of 12-lead ECG results - QRSD interval
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of 12-lead ECG results - QT interval corrected with Fridericia Formula (QTcF)
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Assessment of 12-lead ECG results - RR interval
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Ophthalmic assessment - corrected visual acuity (CVA)
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Ophthalmic assessment - intraocular pressure
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Ophthalmic assessment - light response pupil test
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Ophthalmic assessment - extraocular movement test
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Ophthalmic assessment - slit-lamp examination
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Ophthalmic assessment - corneal fluorescein staining test
timeFrame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Ophthalmic assessment - dilated fundus examination
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - red blood cell distribution width
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - hemoglobin
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - hematocrit
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - red blood cell count
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - white blood cell count
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - absolute neutrophil count
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - neutrophil percentage
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - absolute lymphocyte count
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - lymphocyte percentage
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - absolute monocyte count
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - monocyte percentage
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - absolute basophil count
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - basophil percentage
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - absolute eosinophil count
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - eosinophil percentage
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - platelet count
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - mean cell hemoglobin
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - mean cell volume
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - mean cell hemoglobin concentration
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of hematology results - mean platelet volume
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of coagulation results - international normalized ratio (INR)
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of coagulation results - activated partial thromboplastin time (aPTT)
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of coagulation results - prothrombin time (PT)
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - sodium
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - potassium
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - chloride
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - calcium
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - bicarbonate
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - albumin
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - total protein
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - creatinine
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - creatine kinase
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - estimated glomerular filtration rate (GFR)
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - urea
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - aspartate aminotransferase (AST)
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - alanine aminotransferase (ALT)
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - gamma glutamyl transpeptidase (GGT)
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - alkaline phosphatase (ALP)
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - phosphate
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - total bilirubin
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - direct bilirubin
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - indirect bilirubin
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - amylase
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - cholesterol
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - high density lipoprotein (HDL)/cholesterol ratio
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - high density lipoprotein (HDL) cholesterol
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - low density lipoprotein (LDL) cholesterol/high density lipoprotein (HDL) cholesterol ratio
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - low density lipoprotein (LDL) cholesterol
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - non-high density lipoprotein (HDL) cholesterol
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - triglycerides
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - uric acid
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - lactate dehydrogenase
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - magnesium
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - glucose
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - anion gap
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - adjusted calcium
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of blood biochemistry results - globulin
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of urinalysis results - pH
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of urinalysis results - specific gravity
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of urinalysis results - urine glucose
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of urinalysis results - urine protein
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of urinalysis results - urine bilirubin
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of urinalysis results - urine ketones
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of urinalysis results - urine blood
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of urinalysis results - urine nitrite
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of urinalysis results - urine urobilinogen
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of urinalysis results - leucocyte esterase
timeFrame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of scores of conjunctival hyperemia
timeFrame: From pre-dose to post-dose (Day 2 in Part A, Day 8 in Part B)
measure: Part A and B - Assessment of scores of corneal staining
timeFrame: From pre-dose to post-dose (Day 2 in Part A, Day 8 in Part B)
Secondary outcomes:
measure: Part A - Maximum concentration (Cmax) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
timeFrame: Post-first dose on Day 1 to EOS (Day 7±1 day)
measure: Part A and B - Time to maximum concentration (Tmax) of MDI-1228_mesylate Ophthalmic Solution
timeFrame: Post-first dose on Day 1 to EOS (Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A and B - Half-life (T1/2) of MDI-1228_mesylate Ophthalmic Solution
timeFrame: Post-first dose on Day 1 to EOS (Day 7±1 day in Part A, Day 14±1 day in Part B)
measure: Part A - Systemic clearance (CL or CL/F) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
timeFrame: Post-first dose on Day 1 to EOS (Day 7±1 day)
measure: Part A - Volume of distribution (Vd) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
timeFrame: Post-first dose on Day 1 to EOS (Day 7±1 day)
measure: Part A - Mean retention time (MRT) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
timeFrame: Post-first dose on Day 1 to EOS (Day 7±1 day)
measure: 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
timeFrame: Post-first dose on Day 1 to EOS (Day 7±1 day)
measure: Part A - Area under curve until infinity (AUC0-∞) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
timeFrame: Post-first dose on Day 1 to EOS (Day 7±1 day)
measure: Part B - Trough concentration at steady state (Css_min) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
timeFrame: Post-first dose on Day 1 to EOS (Day 14±1 day)
measure: 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
timeFrame: Post-first dose on Day 1 to EOS (Day 14±1 day)
measure: 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
timeFrame: Post-first dose on Day 1 to EOS (Day 14±1 day)
measure: Part B - Clearance (CL or CL/F) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
timeFrame: Post-first dose on Day 1 to EOS (Day 14±1 day)
measure: 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
timeFrame: Post-first dose on Day 1 to EOS (Day 14±1 day)
measure: Part B - Coefficient of fluctuation (DF) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
timeFrame: Post-first dose on Day 1 to EOS (Day 14±1 day)
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: CMAX Clinical Research
state: South Australia
Study officials:
affiliation: CMAX Clinical Research
name: Sepehr Shakib, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Medinno Pharmaceutical Technology Co., Ltd.
name: Liang Lu, PhD
role: STUDY_DIRECTOR
References: