Clinical Trials/NCT05969236

NCT05969236

Completed

Phase 1

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

Shanghai Medinno Pharmaceutical Technology Co., Ltd.1 site in 1 country40 target enrollmentOctober 6, 2023

ConditionsAllergic Conjunctivitis

InterventionsMDI-1228_mesylate Ophthalmic Solution Placebo

DrugsMDI-1228_mesylate Ophthalmic Solution Placebo

Overview

Phase: Phase 1
Intervention: MDI-1228_mesylate Ophthalmic Solution
Conditions: Allergic Conjunctivitis
Sponsor: Shanghai Medinno Pharmaceutical Technology Co., Ltd.
Enrollment: 40
Locations: 1
Primary Endpoint: Part A and B - Incidence and severity of all systemic or ocular treatment emergent adverse events (TEAEs)
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

October 6, 2023

End Date

May 30, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Shanghai Medinno Pharmaceutical Technology Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.
•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.
•Normal vital signs after ≥ 5 minutes resting supine or semi supine position:
•≥ 90 mmHg and ≤160 mmHg (systolic blood pressure)
•≥50 mmHg and ≤ 95 mmHg (diastolic blood pressure)
•≥ 45 beats per minute (bpm) and ≤ 100 bpm (heart rate)
•Body temperature ≥35.5℃ and ≤37.7℃
•Respiratory Rate≥12 breaths/minute and≤22 breaths/minute
•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.
•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.

Exclusion Criteria

•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.
•Have healed eye disorders (such as infection, trauma) in either eye within 1 month prior to the first dose.
•Have a history of intraocular surgery and laser eye surgery in either eye.
•Used any ocular products (including various eye drops or eye gel) within 14 days or 5 half-lives (whichever is longer) prior to screening.
•Wore contact lenses within 2 days prior to baseline (Day -1) or need to wear contact lenses throughout the clinical study.
•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.
•A positive pre-study HIV, Hepatitis B surface antigen or positive Hepatitis C antibody result at screening.
•Participants who are intolerant of venipuncture blood collection or have poor venous access and/or have a history of fear of needles and hemophobia.
•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.
•Was vaccinated within 2 weeks prior to screening or plan to be vaccinated during the study.

Arms & Interventions

Experimental Group

Including 2 single dose groups (Part A) and 2 multiple dose groups (Part B). Participants in experimental groups will receive MDI-1228_mesylate Ophthalmic Solution.

Intervention: MDI-1228_mesylate Ophthalmic Solution

Comparator Group

One comparator group will be set for each of the 4 experimental groups, to a total of 4 comparator groups. Participants in comparator groups will receive placebo.

Intervention: Placebo

Outcomes

Primary Outcomes

Part A and B - Incidence and severity of all systemic or ocular treatment emergent adverse events (TEAEs)

Time Frame: 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 physical examination results - head, eyes, ears, nose, and throat (HEENT)

Time Frame: 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 - cardiovascular system

Time Frame: 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 vital sign measurement results - respiratory rate

Time Frame: 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 - body temperature

Time Frame: 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 vital sign measurement results - heart rate

Time Frame: 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

Time Frame: 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 physical examination results - neck (including thyroid and nodes)

Time Frame: 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 - respiratory system

Time Frame: 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 - general appearance

Time Frame: 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 - skin

Time Frame: 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

Time Frame: 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 - QRSD interval

Time Frame: 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 QRSD 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 - intraocular pressure

Time Frame: 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 - corneal fluorescein staining test

Time Frame: 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 - Assessment of physical examination results - gastrointestinal system

Time Frame: 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 - neurological system

Time Frame: 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 12-lead ECG results - QT interval corrected with Fridericia Formula (QTcF)

Time Frame: 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

Time Frame: 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 - light response pupil test

Time Frame: 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

Time Frame: 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 - slit-lamp examination

Time Frame: 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 - Assessment of physical examination results - renal system

Time Frame: 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 12-lead ECG results - PR interval

Time Frame: 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 - Ophthalmic assessment - corrected visual acuity (CVA)

Time Frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

CVA (measured using Snellen chart) 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 - Assessment of physical examination results - musculoskeletal system

Time Frame: 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 - Ophthalmic assessment - dilated fundus examination