A Study to Evaluate the Safety and Tolerability of Tirbanibulin Ointment 1% in Adult Participants With Actinic Keratosis

Number of Participants Categorized by Local Tolerability Score by Visit for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration) at Day 29

Local tolerability score was evaluated by investigator in terms of presence and absence of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration signs and its severity in the areas of body where medication was applied. These symptoms were assessed by using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. Number of participants categorized by local tolerability score by visit for each individual signs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) at Day 29 were reported.

Time frame: Baseline, Day 29

Number of Participants Categorized by Local Tolerability Score by Visit for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration) at Day 57

Local tolerability score was evaluated by investigator in terms of presence and absence of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration signs and its severity in the areas of body where medication was applied. These symptoms were assessed by using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. Number of participants categorized by local tolerability score by visit for each individual signs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) at Day 57 were reported.

Time frame: Baseline, Day 57

Number of Participants With Maximum Local Tolerability Score Post-baseline for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration)

Maximum local tolerability score post baseline was defined as the highest grade of any LSR reported at any post-baseline visits for a participant. Local tolerability score was assessed for signs erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. If a participant maximum individual sign local tolerability score stayed at 0 throughout the study, the participant was considered censored at last local tolerability score observation. Number of participants with maximum local tolerability score for each individual signs including erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration were reported.

Time frame: Baseline, Maximum post-baseline (up to Day 57)

Time to Maximum Local Tolerability Score for Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration

Time to maximum local tolerability score (in days) for each individual sign was calculated as \[Date of first post-baseline occurrence of maximum local tolerability score for this individual sign - Date of first dose\]. If a participant maximum individual sign LTA score stays at 0 throughout the study, the participants was considered censored at their last LTA score observation. Maximum local tolerability score was assessed for each signs using a 4 - point scale of 0 - 3, where 0 = absent, 1= mild, 2= moderate and 3 = severe. The higher score indicates severe symptoms. Time to maximum local tolerability score for erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration was reported.

Time frame: Baseline up to Day 57

Local Tolerability Signs Total Composite Score by Visit at Day 5

Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score assessed from baseline up to Day 5 was reported.

Time frame: Baseline, Day 5

Local Tolerability Signs Total Composite Score by Visit at Day 8

Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score by visit at Day 8 was reported.

Time frame: Baseline, Day 8

Local Tolerability Signs Total Composite Score by Visit at Day 15

Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score by visit at Day 15 was reported.

Time frame: Baseline, Day 15

Local Tolerability Signs Total Composite Score by Visit at Day 29

Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score by visit at Day 29 was reported.

Time frame: Baseline, Day 29

Local Tolerability Signs Total Composite Score by Visit at Day 57

Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score by visit at Day 57 was reported.

Time frame: Baseline, Day 57

Maximum Local Tolerability Signs Total Composite Score Post Baseline

The maximum local tolerability signs composite score across visits was derived as the maximum local tolerability composite score observed post-baseline. Local tolerability signs composite score was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Maximum local tolerability signs total composite score post baseline was reported.

Time frame: Baseline, Maximum post-baseline (up to Day 57)

Time to Maximum Local Tolerability Total Composite Score

Time to maximum composite local tolerability score (in days) was calculated as (Date of first post-baseline occurrence of maximum composite local tolerability score - Date of first dose). The maximum local tolerability signs composite score across visits was derived as the maximum local tolerability composite score observed post-baseline. Local tolerability signs composite score was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. If a participant's maximum composite local tolerability score stays at 0 throughout the study, the participant was considered censored at their last local tolerability score observation. Time to maximum local tolerability total composite score was reported.

Time frame: Baseline up to Day 57

Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 5

Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 5 was reported.

Time frame: Baseline, Day 5

Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 8

Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 8 was reported.

Time frame: Baseline, Day 8

Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 15

Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 15 was reported.

Time frame: Baseline, Day 15

Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 29

Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 29 was reported.

Time frame: Baseline, Day 29

Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 57

Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 57 was reported.

Time frame: Baseline, Day 57

Number of Participants With Any Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)

TEAEs were defined as either those adverse events (AEs) with an onset after dosing or those pre-existing conditions that worsened after dosing. An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an Investigational Product. An SAE with any untoward medical occurrence that at any dose, resulted in death, was life-threatening, 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, or any other medically important event that may jeopardize the patient or require intervention to prevent one of the other outcomes. AESI's included in this study were skin cancers (including basal cell carcinoma, squamous cell carcinoma, and melanoma) based on their relevance for the current intended use. TEAEs included both serious and non-serious AEs.

Time frame: Baseline up to Day 57

Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters

Laboratory parameters included blood chemistry, hamatology, and urinalysis. Clinically significant laboratory abnormalities assessment was based on Investigator interpretation. Number of participants with clinically significant abnormalities in laboratory parameters (included hematology, blood chemistry and urinalysis) were reported.

Time frame: Baseline up to Day 57

Number of Participants With Clinically Significant Abnormalities in Vital Signs

Vital signs included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Clinically significant vital signs abnormalities assessment was based on Investigator interpretation. Number of participants with clinically significant abnormalities in vital signs were reported.

Time frame: Baseline up to Day 57

Number of Participants With Clinically Significant Abnormalities in Physical Examination

Physical examination included weight and height measurements. Clinically significant physical examination abnormalities assessment was based on Investigator interpretation. Number of participants with clinically significant abnormalities in physical examination were reported.

Time frame: Baseline up to Day 57

Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)

ECG included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals parameters measurement. Clinically significant ECGs abnormalities assessment was based on Investigator interpretation. Number of participants with clinically significant abnormalities in ECG were reported.

Time frame: Baseline up to Day 57