Tolerability, Safety and Pharmacokinetics of a Topical AB001 Patch in Healthy Subjects

Study Overview
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Brief Summary
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The study evaluates the safety, tolerability and pharmacokinetics of single and repeated doses of topical AB001 patch and the bioavailability relative to the oral capsule and topical positive comparative patch.

Detailed Description
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Eligible subjects will be randomly assigned to Treatment goup A, B and C. In the experiment group A, 12 subjects with a ratio of 10:2 will receive one patch of AB001 or placebo batch on Day 1 of period 1, respectively, after a wash-out period of 14 days, 10 subjects received AB001 patch will be administered with an oral capsule of active ingredient on Day 20 of period 2. In the experiment group B, 12 subjects with a ratio of 10:2 will receive two patches of AB001 or two placebo batches on Day 1 respectively, and then two patches daily from Day 8 to Day 20. In the active comparator group C, 10 subjects will receive one patch of positive comparative patch on Day 1, and then once patch every two days from Day 8 to Day 20. The tolerability, safety and pharmacokinetics of topical AB001 patch will be assessed in this study.

Official Title
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A Phase 1, Placebo-controlled, Randomized, Parallel Group Study to Evaluate the Tolerability, Safety and Pharmacokinetics of a Topical Patch AB001 Following Single and Repeated Administration in Healthy Subjects

Conditions
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Chronic Low Back Pain

Intervention / Treatment
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* Drug: AB001
* Drug: oral capsule
* Drug: positive comparative patch
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects between 18 and 45 years with a BMI of 18 to 30 kg/m2, inclusive, and weigh at least 45 kg. Subjects having normal skin without excessive hair growth on tested areas. Evidence of a personally signed and dated informed consent document indicating that the subjects has been informed of all pertinent aspects of the trial. Subjects who are willing to comply with scheduled visits and other trial procedures Exclusion Criteria: A history or presence of significant cardiovascular, neurological, hematological, psychiatric, infectious, hepatic, gastrointestinal, pulmonary, endocrine, immunologic or renal disease or other conditions known to interfere with the topical absorption, distribution, metabolism, or excretion of drugs or place the subjects at increased risk as determined by the investigator History of hypersensitivity to NSAIDs Clinically significant laboratory abnormalities as judged by the investigator Known sensitivity to adhesive tape, component of the test products or topically applied products Any active malignancy Suffering from severe acne, moderate to severe hirsutism or androgenic alopecia Any chronic skin disorder (e.g., eczema, psoriasis) likely to interfere with transdermal drug absorption or assessment of skin tolerability Skin abnormalities likely to be aggravated by the study medication, such as dermatological diseases or infections, rash, skin sensitive to topical preparations or adhesive dressings Pregnant and/or nursing women Any visible skin disorder or abnormal skin pigmentation which, in the opinion of the investigator, would interfere with the outcome of the trial History of alcohol or drug abuse within 18 months Blood donation or significant blood loss within 60 days of dosing or plasma donation within 7 days of dosing Use of any medication within 4 weeks prior to the first treatment or during the trial, which in the opinion of the investigator may influence the trial results or the safety of the subjects Subjects who cannot avoid, throughout the duration of the trial, any swimming, any washing of the back, and sauna or any intense physical activity that might result in excessive sweating Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy.

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: Treatment A-AB001<br>Apply 1 patch of AB001 patch on the lower back of the subjects on either side of the spine without occlusion for 12 hours on Day 1 in period 1. Subjects who received the AB001 patch in period 1 will then receive a single oral capsule of active ingredient on Day 20 in period 2. | Drug: AB001<br>* single and repeated dosing<br>* Other names: topical patch;Drug: oral capsule<br>* single dose<br>* Other names: active ingredient;|
| Experimental: Treatment B-AB001<br>Apply 2 patches of AB001 patches on the lower back of the subjects on side of the spine without occlusion for 12 hours on Day 1 and then once daily from Day 8 to 20. | Drug: AB001<br>* single and repeated dosing<br>* Other names: topical patch;|
| Active Comparator: Treatment C<br>Apply 1 patch of positive comparative patch on the lower back of the subjects on either side of the spine without occlusion for 48 hours on Day 1 and then one patch every two days from Days 8 to 20. | Drug: positive comparative patch<br>* single and repeated dosing<br>* Other names: topical patch;|
| Placebo Comparator: Treatment A-Placebo<br>Apply 1 patch of placebo patch on the lower back of the subjects on either side of the spine without occlusion for 12 hours on Day 1 in period 1. | Drug: Placebos<br>* single and repeated dosing<br>* Other names: topical patch;|
| Placebo Comparator: Treatment B-Placebo<br>Apply 2 patches of placebo patches on the lower back of the subjects on side of the spine without occlusion for 12 hours on Day 1 and then once daily from Day 8 to 20. | Drug: Placebos<br>* single and repeated dosing<br>* Other names: topical patch;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with any adverse events (AEs) | An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | From baseline through Day 26 | 
| Number of subjects any serious adverse events (SAEs) | An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect. | From baseline through Day 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Assessments on Skin Reaction Evaluation | Topical Skin Reaction Score(0-2 is a better outcome): 0= no evidence of irritation minimal erythema, barely perceptible definite erythema, readily visible; minimal edema or minimal papular response erythema and papules definite edema erythema, edema and papules vesicular eruption strong reaction spreading beyond application site | From baseline through Day 26 | 
| pharmacokinetic parameters of AB001(Cmax) | Peak Plasma Concentration (Cmax) | Day 1 and Day 26 | 
| pharmacokinetic parameters of AB001 (AUC) | Area under the plasma concentration versus time curve (AUC) | Day 1 and Day 26 | 
| bioavailability of AB001 | To determine the bioavailability of AB001 | Day 1 and Day 26 |