Ph 1, Single-Center, Safety, Tolerability & Pharmacokinetic Study of KX2 391 Ointment in Subj. w Actinic Keratosis

Study Overview
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Brief Summary
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This is a phase 1 study to access the safety and tolerability of KX2-391 ointment in subjects who have Actinic Keratosis. This study will also access the amount of KX2-391 drug that enters the blood stream through dermal application of the ointment.

Official Title
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A Phase 1, Single-Center, Safety, Tolerability, and Pharmacokinetic Study of KX2 391 Ointment in Subjects With Actinic Keratosis

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: KX2-391 Ointment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is at least 18 years old Subject has a clinical diagnosis of stable, clinically typical AK Subject has a treatment area on 1 dorsal forearm that in: Cohort 1: Is one contiguous area Measures 25 cm2 Contains 4 to 8 AK lesions that are clinically typical. Cohort 2: Is one contiguous area Measures 100 cm2 Contains 8 to 16 AK lesions that are clinically typical. All women of childbearing potential (WOCBP) must be: Post-menopausal, defined as at least 50 years of age with amenorrhea for at least 18 months, or Surgically sterile, defined as having undergone a hysterectomy, bilateral oophorectomy or tubal ligation, or otherwise incapable of pregnancy. Pre or perimenopausal and practicing a highly effective method of birth control, including hormonal prescription, oral contraceptives, contraceptive injections, contraceptive patch, and intrauterine device, for the duration of their participation in the study. Abstinence and double-barrier methods do not qualify as highly effective methods of birth control. All woman of child-bearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 (Visit 2) prior to administration of KX2-391 Ointment dose. Contraception Contraception must be consistently used for at least 3 months prior to screening to 3 months after the last KX2-391 Ointment dose. Male Contraception: All men who are sexually active with female partners of child bearing potential must agree to ensure their partners use highly effective contraception and therefore will not father a child from screening to 3 months after the last dose of study medication. Male and Female Contraception: All men and women subjects must agree to not donate sperm or eggs or attempt conception from screening to 3 months after the last KX2-391 Ointment dose. Subject is, in the opinion of the investigator, in good general health based on medical history, physical examination, electrocardiogram (ECG), and clinical laboratory evaluations at screening. Subject has clinically acceptable liver function at screening as demonstrated by: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2x upper limit of normal (ULN) Total bilirubin ≤ ULN No other screening laboratory test, including CBC results, considered clinically significant by the investigator Subject is not lactating Subject is willing and able to follow all study instructions and to attend all study visits Subject is able to comprehend and willing to sign an Informed Consent Form (ICF) Exclusion Criteria: Subject has clinically atypical and/or rapidly changing AK lesions on the treatment area Subject has current systemic malignancy Subject has used any of the following systemic therapies within the specific period before Visit 1: Retinoids; 180 days Glucocortico-steroids; 28 days Methotrexate or other anti-metabolites; 28 days Subject has used any of the following topical therapies on the treatment area within the specified period before Visit 1: Retinoids; 90 days Glucocortico-steroids; 14 days Subject has had any of the following of the AK therapies on the treatment area: Medical Therapies within 90 days (or until the site has healed, whichever is longer) before Visit 1: Ingenol mebutate (eg, Picato) 5-fluorouracil (eg, 5-FU; Efudex) Imiquimod (eg, Aldara; Zyclara) Diclofenac with or without hyaluronic acid (eg, Solaraze) Moisturizer, emollients (12 hours prior to Visit 1) Surgical Modalities on the treatment area within 30 days (or until the site has healed following treatment, whichever is longer) before Visit 1: Cryotherapy Electrodesiccation Laser, light (eg, photodynamic therapy, intense pulsed light) or any other energy based therapy Chemical peels (eg, tricholoracetic acid) Dermabrasion Surgical removal (eg, curettage, excision) Subject currently has, or has experienced any of the following on the treatment area within the specified period before Visit 1: A cutaneous malignancy; 180 days Sunburn; 28 days Body art (eg, tattoo, piercing); currently Excessive tan; currently Subject has a history of sensitivity to any of the ingredients in the study medications Subject is chronically taking a known strong inhibitor of CYP3A4 Subject has a skin disease (eg, atopic dermatitis, psoriasis, eczema) or condition (eg, scarring, open wounds) that, in the opinion of the investigator, might interfere with the study conduct or evaluations, or which exposes the subject to an unacceptable risk by study participation. Subject has other significant uncontrolled or unstable medical diseases or conditions that, in the opinion of the investigator, would expose the patient to unacceptable risk from study participation. Subject has participated in an investigational drug trial during which an investigational study medication was administered within 30 days before Visit 1.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KX2-391 Ointment<br> | Drug: KX2-391 Ointment<br>* KX2-391 Ointment will be applied at a predetermined concentration to the treatment area for a predetermined time period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall safety and tolerability assessment as determined by laboratory, adverse event (AE) and serious adverse event (SAE) information. | Safety assessments will consist of determining and recording all AEs (including for both increasing and decreasing severity) and SAEs; laboratory evaluation for hematology, blood chemistry, and urine analytes; periodic measurement of vital signs and ECGs; and the performance of physical examinations as detailed in Table 3 of the protocol. | 45 days | 
| The amount of KX2-391 in the blood stream as determined by pharmacokinetic (PK) analysis: Cmax, Cmin, AUC0-t, AUC0-inf | Individual PK data will be listed by time. Cmax, Cmin, AUC0-t, AUC0-inf will be calculated for KX2-391 to determine systemic exposure. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actinic Keratosis (AK) lesion count | The AK lesion count is the investigator's assessment of the number of AK lesions in the treatment area. | 45 days |