Study of X0002 Following Escalating Single and Multiple Doses Administered as Topical Application in Healthy Volunteers

Study Overview
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Brief Summary
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Primary Objectives: To evaluate the safety and tolerability of escalating single and multiple doses of X0002 administered as a topical application. Secondary Objectives: To characterize the single and and multiple pharmacokinetics of escalating doses of X0002 and its active metabolite ibuprofen as a topical application.

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: X0002
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gender: male or female, each sex ratio does no less 1/3; Were between the ages of 18 and 45 years, inclusive. General condition is will; Were between the Body Mass Index (BMI) of 19-28, inclusive; BMI=Weight(kg)/Height2 (m2); Weight≥50kg (female) and 60kg (male); Nearly half of the year, no child care program and agree to take effective measures to contraception during the study period, blood pregnancy test of women in childbearing age was negative; Vital signs (measurement seated after resting 5 minutes) in the following range Temperature (auxiliary temperature): 35.0-37.0℃ Systolic Pressure: 90-139mmHg Diastolic Pressure: 60-89mmHg sphygmus: 55-99bpm Subjects to fully understand the purpose, properties, method and reactions may occur of test drug trials. Were capable of giving informed consents voluntarily, and agreed to comply with the requirements of clinical protocols. Exclusion Criteria: Primary disease in important organs; Mental or physical disability; Familial hereditary diseases; Clinically significant history of Electrocardiograph (ECG) abnormality, or Electrocardiograph (ECG) abnormality in the Screening or Baseline; Clinically significant abnormities in laboratory examination: Clinically significant abnormities in Liver Function Tests, for example aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) or bilirubin. Creatinine and Urea Nitrogen exceeded the upper limit of normal, or significant abnormities in urinary composition. Clinically significant abnormities of routine blood test, for example anemia, Leukocyte reduced, Platelet significantly reduced,etc.( Combined with adverse events in the laboratory to determine the value of abnormal). Abnormality of immunology, including HIV(human immunodeficiency virus) antibody positive, Hepatitis B surface antigen (HBsAg) positive, HCV(hepatitis C virus) antibody positive or Syphilis antibody positive. Drug abusers,or drug screening positive; Who was addicted to alcohol and tobacco (drinking 14 units of alcohol per week: 1 unit = beer 285 ml, or liquor 25 ml, or wine 1 cup. numbers of daily smoking ≥ 5) and / or not smoking and drinking in the test period;Test positive for nicotine or breath test positive for alcohol(>0.0mg/100ml); Took any drug long excretory phase that may affect the study, or in the past 3 months participated in any drug clinical trials; Entering the group 4 weeks ago used any prescription drugs ,or used any over the counter (OTC) drugs within 2 weeks (vitamins, herbal tonics, etc.), or before entering the group within 2 weeks took excessively food that effected drug metabolizing enzymes, such as grapefruit or grapefruit drink. Can the use of acetaminophen, but must record report in case report form (CRF）; A history of gastrointestinal bleeding or peptic ulcers, drugs allergy for aspirin or hypersensitivity to aspirin or other NSAIDs (Non-Steroidal Antiinflammatory Drugs), or a history of asthma or other allergic-type reactions after taking aspirin or other NSAIDs(Non-Steroidal Antiinflammatory Drugs); A history of intolerance or hypersensitivity to ibuprofenamine hydrochloride or any excipients or to the diluent ethanol; Donation or blood collection, or acute loss of blood during the 3 months prior to screening( more than 400ml); Had skin diseases wound or other symptom, investigators consider that maybe unsafe for subjects or effect of evaluation for application sites; There was a clinical significance history of allergy for drugs or food, or atopic allergic diseases (asthma, urticaria, eczema dermatitis) or a known drug allergy for test drugs or similar drugs; Lactating women, pregnant women or unable to take effective contraceptive measures; Researchers believed that participants not suitable to take the test for other factors.

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: X0002 First Dose<br>Preliminary Experiment,4 Subjects,Single-Dose,Once,Non-Blind. | Drug: X0002<br>* External Spray<br>|
| Experimental: X0002 Second Dose<br>8 Subjects,Single Dose once and Multiple Doses 7 Days,b.i.d,12 Hours Apart,Double-Blind. | Drug: X0002<br>* External Spray<br>|
| Placebo Comparator: Placebo Second Dose<br>2 Subjects,Single Dose once and Multiple Doses 7 Days,b.i.d,12 Hours Apart,Double-Blind. | Drug: Placebo<br>* External Spray<br>|
| Experimental: X0002 Third Dose<br>8 Subjects,Single Dose once and Multiple Doses 7 Days,b.i.d,12 Hours Apart,Double-Blind. | Drug: X0002<br>* External Spray<br>|
| Placebo Comparator: Placebo Third Dose<br>2 Subjects,Single Dose once and Multiple Doses 7 Days,b.i.d,12 Hours Apart,Double-Blind. | Drug: Placebo<br>* External Spray<br>|
| Experimental: X0002 Fourth Dose<br>8 Subjects,Single Dose,Once,Double-Blind. | Drug: X0002<br>* External Spray<br>|
| Placebo Comparator: Placebo Fourth Dose<br>2 Subjects,Single Dose,Once,Double-Blind. | Drug: Placebo<br>* External Spray<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Adverse Event; Vital Signs; Physical Examination; Laboratory Examination; Electrocardiograph; Skin Irritation | Single Dose Arms:6days;Multiple Doses Arms:17days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters(Maximum Plasma Concentration [Cmax]) |  | Single Dose Arms:0-120hours;Multiple Doses Arms:0-120hours post-dose;11th day pre-dose;12th day 0-120 hours post-dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis