A First-in-Human Study of QY101 Ointment in Adult Subjects

Study Overview
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Brief Summary
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This is a phase I, randomized, double-blind, vehicle-controlled，single and multiple ascending dose study to assess the safety, tolerability, and pharmacokinetics of QY101 ointment in Chinese healthy subjects

Official Title
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This is a Phase I, Randomized, Double-blind, Vehicle-controlled Study of QY101 Ointment in Chinese Healthy Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: QY101 ointment or vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subjects were fully aware of the purpose, nature, methods and possible adverse reactions of the trial, volunteered as subjects, and signed an informed consent form before the start of any research process. Male and female subjects aged 18 to 45 (including 18 and 45). Male weight≥50.0 kg, female weight≥45.0 kg; BMI is in the range of 19.0   26.0 kg/ m2 (including the critical value). The subjects had no history of chronic or serious diseases such as cardiovascular, liver, kidney, respiration, blood and lymph, endocrine, immune, mental, nervous, gastrointestinal system, and were in good health. Physical examination, vital signs, clinical laboratory examination values (blood routine, urine routine, blood biochemistry, blood coagulation function, stool routine and occult blood, pregnancy test (female), hepatitis, HIV, syphilis), 12-lead ECG, chest X-ray examination, abdominal ultrasound examination results are all within the normal range or abnormalities with no clinical significance. The subjects (including male subjects) had no fertility plan, voluntary use of effective contraception and no plan to donate sperm or eggs during the screening period and within 6 months after the end of the last administration. The subjects were able to communicate well with the researchers and understand and comply with the requirements of this study. Exclusion Criteria: Allergic constitution, such as a history of allergy to two or more drugs and food, or those known to be allergic to QY101 and excipients. Screen those who have undergone surgery within the previous 3 months, or who plan to undergo surgery during the study period, or who have undergone surgery that will affect the absorption, distribution, metabolism and excretion of drugs. Diseases that need to be excluded with abnormal clinical manifestations, including, but not limited to, diseases of the nervous system, cardiovascular system, blood and lymphoid system, immune system, kidney, liver, gastrointestinal tract, respiratory system, metabolic and skeletal system, etc. Subjects who cannot tolerate venipuncture, have a history of dizzy needles and blood sickness. Subjects with a history of severe skin disease (subject to the judgment of the researcher). Live (attenuated) vaccine was vaccinated within 2 months before screening. Smoking or drinking within 3 months before screening (smoking: > 10 cigarettes per day; drinking: > 15g pure alcohol per day, equivalent to 450mL beer, 150mL wine or 50mL low alcohol), or positive for nicotine, alcohol, abuse drugs (morphine / methamphetamine / ketamine / dimethylene dioxyamphetamine / tetrahydrocannabinic acid). Screen subjects who have participated in other drug clinical trials or have not come to participate in clinical trials within the first 3 months. Non-physiological blood loss ≥ 200ml within 3 months before screening (including trauma, blood collection, blood donation), or plan to donate blood during the study period or within 1 month after the end of the study. The subjects (female) are lactating. Strong inhibitors or inducers of CYP3A liver metabolic enzymes were used in the previous 2 weeks (see Appendix 2 for details), or any drugs, including prescription, over-the-counter and herbal medicines, were used for oral or topical use, except vitamins and / or paracetamol. To screen subjects who drank too much tea, coffee and / or caffeinated beverages (more than 8 cups, 1 cup = 250mL) every day for the first 3 months. Subjects with abnormal vital signs were included in the standard reference range (including critical value): sitting systolic blood pressure 90 139mmHg, diastolic blood pressure 55-89mmHg, pulse 55-100bpm, body temperature 36.037.4C, breathing 12-22bpm; if the subject's first examination result is abnormal, retest can be carried out after rest. There are tattoos, birthmarks, sunburns, abrasions, ulcers, erythema, dryness, scabs and scars in the target area (back, abdomen and lower limbs from thigh to calf) of the subjects. Subjects determined by other researchers to be unfit to participate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAD Cohort 1(0.1% QY101 ointment or vehicle apply to 5%BSA)<br>3 subjects use 0.1% QY101 ointment，1 subject uses vehicle topical applied to 5% Body Surface Area，assessed until 72 hours postdose | Drug: QY101 ointment or vehicle<br>* QY101 ointment or vehicl topical applied to skin<br>|
| Experimental: SAD Cohort 2(0.1% QY101 ointment or vehicle apply to 20%BSA)<br>6 subjects use 0.1% QY101 ointment，2 subjects use vehicle topical applied to 20% Body Surface Area，assessed until 72 hours postdose | Drug: QY101 ointment or vehicle<br>* QY101 ointment or vehicl topical applied to skin<br>|
| Experimental: SAD Cohort 3(0.3% QY101 ointment or vehicle apply to 20%BSA)<br>6 subjects use 0.3% QY101 ointment，2 subjects use vehicle topical applied to 20% Body Surface Area，assessed until 72 hours postdose | Drug: QY101 ointment or vehicle<br>* QY101 ointment or vehicl topical applied to skin<br>|
| Experimental: SAD Cohort 4(0.5% QY101 ointment or vehicle apply to 20%BSA)<br>6 subjects use 0.5% QY101 ointment，2 subjects use vehicle topical applied to 20% Body Surface Area，assessed until 72 hours postdose | Drug: QY101 ointment or vehicle<br>* QY101 ointment or vehicl topical applied to skin<br>|
| Experimental: SAD Cohort 5(1.0% QY101 ointment or vehicle apply to 20%BSA)<br>6 subjects use 1.0% QY101 ointment，2 subjects use vehicle topical applied to 20% Body Surface Area，assessed until 72 hours postdose | Drug: QY101 ointment or vehicle<br>* QY101 ointment or vehicl topical applied to skin<br>|
| Experimental: SAD Cohort 6(1.0% QY101 ointment or vehicle apply to 40%BSA)<br>6 subjects use 1.0% QY101 ointment，2 subjects use vehicle topical applied to 40% Body Surface Area，assessed until 72 hours postdose | Drug: QY101 ointment or vehicle<br>* QY101 ointment or vehicl topical applied to skin<br>|
| Experimental: MAD Cohort 7(0.3% QY101 ointment or vehicle apply to 20%BSA)<br>6 subjects use 0.3% QY101 ointment，2 subjects use vehicle topical applied to 20% Body Surface Area，twice daily for 7 days and once in the morning on D8 | Drug: QY101 ointment or vehicle<br>* QY101 ointment or vehicl topical applied to skin<br>|
| Experimental: MAD Cohort 8(0.5% QY101 ointment or vehicle apply to 20%BSA)<br>6 subjects use 0.5% QY101 ointment，2 subjects use vehicle topical applied to 20% Body Surface Area，twice daily for 7 days and once in the morning on D8 | Drug: QY101 ointment or vehicle<br>* QY101 ointment or vehicl topical applied to skin<br>|
| Experimental: MAD Cohort 9(1.0% QY101 ointment or vehicle apply to 20%BSA)<br>6 subjects use 1.0% QY101 ointment，2 subjects use vehicle topical applied to 20% Body Surface Area，twice daily for 7 days and once in the morning on D8 | Drug: QY101 ointment or vehicle<br>* QY101 ointment or vehicl topical applied to skin<br>|
| Experimental: MAD Cohort 10(1.0% QY101 ointment or vehicle apply to 40%BSA)<br>6 subjects use 1.0% QY101 ointment，2 subjects use vehicle topical applied to 40% Body Surface Area，twice daily for 7 days and once in the morning on D8 | Drug: QY101 ointment or vehicle<br>* QY101 ointment or vehicl topical applied to skin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | SAD：Day1 to Day18；MAD：Day1 to Day25 | 
| Number of Participants With Clinical Laboratory Abnormalities |  | SAD：Screening period and Day4；MAD：Screening period, Day5 and Day11 | 
| Number of Participants With Clinically Significant Changes Form Baseline in Vital Signs |  | SAD：Screening period and Day1 to Day4；MAD：Screening period and Day1 to Day11 | 
| Severity of local skin irritation | Skin irritation response assessment recording method: -: no reaction; + (mild): only erythema can be observed; + (moderate): moderate erythema, edema; + (severe): severe erythema, edema with papules, vesicles; + (severe): severe erythema, edema, bullae, and even necrosis. | SAD：Day1 to Day4；MAD：Day1 to Day11 | 
| Number of Participants With Clinically Significant Treatment-emergent Electrocardiogram (ECG) Findings |  | SAD：Screening period and Day4；MAD：Screening period, Day5 and Day11 | 
| Number of Participants With Clinically Significant Changes Form Baseline in Physical Examination |  | SAD：Screening period and Day4；MAD：Screening period, Day5 and Day11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax of QY101 | Time of maximum concentration | SAD：Day1 to Day4；MAD：Day1，Day5 to Day11 | 
| Cmax of QY101 | Maximum observed plasma concentration | SAD：Day1 to Day4；MAD：Day1，Day5 to Day11 | 
| t1/2 of QY101 | The time it takes for the blood concentration of the drug to drop by half from the highest value in the body | SAD：Day1 to Day4；MAD：Day1，Day5 to Day11 | 
| AUC0-∞ of QY101 | Area under the plasma concentration-time curve from time zero to the last quantifiable concentration | SAD：Day1 to Day4；MAD：Day1，Day5 to Day11 |