Activity & Safety Study of KX2-391 Ointment in Participants With Actinic Keratosis on the Face or Scalp
- Conditions
- Actinic Keratosis
- Interventions
- Drug: 50 mg of KX2-391 Ointment 1%
- Registration Number
- NCT02838628
- Lead Sponsor
- Almirall, S.A.
- Brief Summary
In this study, the activity, safety, and pharmacokinetics (PK) of KX2-391 Ointment was evaluated in adult participants with a clinical diagnosis of stable, clinically typical actinic keratosis (AK) on the face or scalp.
- Detailed Description
This study was an open-label, multicenter, activity, safety, tolerability, and PK study of KX2-391 Ointment administered topically to the face or scalp of participants with AK.
The study consists of Screening, Treatment, and Follow-up Periods. Eligible participants were received 3 or 5 consecutive days of topical treatment, applied at the study site. Blood samples for PK analysis were collected. Activity (lesion counts) and safety evaluations were performed.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 168
- Males and females ≥18 years old
- Clinical diagnosis of stable, clinically typical actinic keratosis
- A define treatment area on the face or scalp
- Females must be postmenopausal, surgically sterile or otherwise incapable of pregnancy for at least 1 year; or must be using highly effective contraception for at least 90 days prior to treatment with KX2-391 Ointment
- Males who have not had a vasectomy must agree to use barrier contraception
- Participants who in the judgment of the Investigator, are in good general health
- Willing to avoid excessive sun exposure
- Able to comprehend and are willing to sign an informed consent form (ICF)
- Clinically atypical and/or rapidly changing AK lesions on the treatment area
- Malignancy within 5 years prior to Screening except basal or squamous cell carcinoma not on the treatment area that were treated with curative intent and are without recurrence
- Used any of retinoids at the most 90 days before Visit 1 glucocorticosteroids and methotrexate or other anti-metabolites within, at the most 28 days, before Visit 1
- Used any topical therapies, treatments, or surgical or destructive modalities on the treatment area within, at the most 90 days, before Visit 1
- Currently, or has experienced cutaneous malignancy, sunburn or body art on the treatment area within, at the most 180 days, before Visit 1
- A history of sensitivity and/or allergy to any of the ingredients in the study medication
- A skin disease or condition that, in the opinion of the Investigator, might interfere with the study conduct or evaluations, or which exposes the participant to an unacceptable risk by study participation
- Other significant uncontrolled or unstable medical diseases or conditions that, in the opinion of the Investigator, would expose the participant to unacceptable risk by study participation
- Females who are pregnant or nursing
- Participated in an investigational drug trial during which an investigational study medication was administered within 14 days or 5 half-lives of the investigational product, whichever is longer, before dosing.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description KX2-391 50 mg (Days 1 to 5) 50 mg of KX2-391 Ointment 1% Participants were applied 50 milligrams (mg) of KX2-391 Ointment 1% topically on face or scalp in 25 centimeter square (cm\^2) treatment area, once daily for 5 consecutive days. KX2-391 50 mg (Days 1 to 3) 50 mg of KX2-391 Ointment 1% Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 3 consecutive days.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Complete Response of Actinic Keratosis Day 57 Complete response rate was defined as the percentage of participants achieving 100% clearance in the treatment area on the face or scalp at Day 57.
- Secondary Outcome Measures
Name Time Method Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) Baseline up to Day 57 (Treatment and follow-up period) An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational Product (IP). An AE did not necessarily have a causal relationship with the medicinal product. An SAE was defined as any untoward medical occurrence that at any dose, resulted in death, was life-threatening (i.e, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). TEAEs were defined as either those AEs with an onset after dosing or those pre-existing conditions that worsened after dosing. TEAEs included both serious and non-serious TEAEs.
Number of Participants With Any Treatment-emergent Adverse Events During Recurrence Follow-up Period From Day 57 up to 12-months post-Day 57 (Recurrence follow-up period) An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an IP. An AE did not necessarily have a causal relationship with the medicinal product. An SAE was defined as any untoward medical occurrence that at any dose, resulted in death, was life-threatening (i.e, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). TEAEs were defined as either those AEs with an onset after dosing or those pre-existing conditions that worsened after dosing. TEAEs included both serious and non-serious TEAEs.
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Day 57 Maximal post baseline LSR was defined as the highest grade of any LSR reported at any post baseline visits for a participant. Local skin reactions assessment included signs of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration on the treatment area. These signs were assessed using a 5-point grading scale ranging from 0 (not present) to 4 (worst), where (grade 0 = absent, grade 1 = slight, grade 2 = moderate, grade 3 = severe, grade 4 = very severe).
Number of Participants With Clinically Significant Abnormalities in Vital Signs Baseline up to Day 57 Vital signs included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Clinical significance was determined by the investigator.
Number of Participants With Clinically Significant Abnormalities in Physical Examination (PE) Baseline up to Day 57 A physical examination included weight and height measurements was performed. Clinical significance was determined by the investigator.
Accumulation Ratio (R) Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1) Ratio calculated from AUC and Cmax found on the last day of treatment and Day 1.
Overall Change From Baseline in Actinic Keratosis Lesion Counts at Day 8, 15, 29 and 57 Baseline, Days 8, 15, 29 and 57 Overall changes from baseline in actinic keratosis lesion counts has been reported.
Number of Participants With Clinically Significant Abnormalities in Laboratory Baseline to Day 57 Laboratory parameters included hematology, blood chemistry and urinalysis. Clinical significance was determined by the investigator.
Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) Baseline up to Day 57 ECG parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals. Clinical significance was determined by the investigator.
Percentage of Participants With Partial Response of Actinic Keratosis Day 57 Partial response rate was defined as the percentage of participants achieving more than or equal to 75% clearance in the treatment area on the face or scalp at Day 57.
Maximum Observed Plasma Concentration (Cmax) of KX2-391 of KX2-391 Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1) Cmax was defined as the maximum observed plasma concentration obtained directly from the concentration versus time curve.
Area Under the Plasma Concentration Time Curve From Time 0 to the Last Sampling Time (AUCt) of KX2-391 Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1) Area under the plasma concentration versus time curve from time zero to the last sampling time (t) at which the concentration is at or above the LLOQ. AUC(0-t) was calculated according to the mixed log-linear trapezoidal rule.
Minimum Observed Plasma Concentration (Cmin) of KX2-391 Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1) Cmin was defined as minimum observed plasma concentration obtained directly from the concentration versus time curve.
Trial Locations
- Locations (16)
International Dermatology Research
🇺🇸Miami, Florida, United States
The Center for Skin Research
🇺🇸Houston, Texas, United States
Clinical Trials of Texas, Inc.
🇺🇸San Antonio, Texas, United States
Palm Beach Research Center
🇺🇸West Palm Beach, Florida, United States
Center for Dermatology Clinical Research
🇺🇸Fremont, California, United States
eStudy Site
🇺🇸La Mesa, California, United States
Palmtree Clinical Research, Inc.
🇺🇸Palm Springs, California, United States
Horizons Clinical Research Center
🇺🇸Denver, Colorado, United States
Forward Clinical Trials, Inc.
🇺🇸Tampa, Florida, United States
Dermatology and Laser Center of Charleston
🇺🇸Charleston, South Carolina, United States
Compass Research
🇺🇸Orlando, Florida, United States
Clinical Research of South Florida
🇺🇸Coral Gables, Florida, United States
Minnesota Clinical Study Center
🇺🇸Fridley, Minnesota, United States
Institute of Clinical Research - Tennessee, LLC
🇺🇸Murfreesboro, Tennessee, United States
J&S Studies, Inc.
🇺🇸College Station, Texas, United States
Dermatology Clinical Research Center
🇺🇸San Antonio, Texas, United States