Trial Outcomes & Findings for Activity & Safety Study of KX2-391 Ointment in Participants With Actinic Keratosis on the Face or Scalp (NCT NCT02838628)

Last Updated: 2021-04-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

168 participants

Primary outcome timeframe

Day 57

Results posted on

2021-04-14

Participant Flow

This study was conducted at 16 sites in United States from 11 April 2016 to 22 December 2017.

A total of 168 participants (84 each cohort) were enrolled and treated in this study. This study consisted of 2 periods, first was Treatment and Follow-up period (up to Day 57) and second was Recurrence follow-up period (12 months post-Day 57).

Participant milestones

Participant milestones
Measure	KX2-391 50 mg (Days 1 to 5) 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) 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.
Treatment and Follow-up Period STARTED	84	84
Treatment and Follow-up Period COMPLETED	84	84
Treatment and Follow-up Period NOT COMPLETED	0	0
Recurrence Follow-up Period STARTED	36	27
Recurrence Follow-up Period COMPLETED	16	10
Recurrence Follow-up Period NOT COMPLETED	20	17

Reasons for withdrawal

Reasons for withdrawal
Measure	KX2-391 50 mg (Days 1 to 5) 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) 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.
Recurrence Follow-up Period AK Recurrence	18	13
Recurrence Follow-up Period Adverse Event	1	0
Recurrence Follow-up Period Non-compliance	0	1
Recurrence Follow-up Period Withdrawal by Subject	0	2
Recurrence Follow-up Period Other un-specified	1	1

Baseline Characteristics

Activity & Safety Study of KX2-391 Ointment in Participants With Actinic Keratosis on the Face or Scalp

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.	Total n=168 Participants Total of all reporting groups
Age, Continuous	69.0 Years STANDARD_DEVIATION 8.93 • n=5 Participants	67.7 Years STANDARD_DEVIATION 8.32 • n=7 Participants	68.3 Years STANDARD_DEVIATION 8.63 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	76 Participants n=5 Participants	72 Participants n=7 Participants	148 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	81 Participants n=5 Participants	75 Participants n=7 Participants	156 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	84 Participants n=5 Participants	83 Participants n=7 Participants	167 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Number of AK Lesions	5.8 Lesions STANDARD_DEVIATION 1.41 • n=5 Participants	5.4 Lesions STANDARD_DEVIATION 1.19 • n=7 Participants	5.6 Lesions STANDARD_DEVIATION 1.32 • n=5 Participants

PRIMARY outcome

Timeframe: Day 57

Population: Evaluable set included group of protocol-eligible participants who received 5 days (Cohort 1) or 3 days (Cohort 2) of study treatment and completed Day 1 and Day 57 AK lesion evaluations.

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.

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.
Percentage of Participants With Complete Response of Actinic Keratosis	43 percentage of participants Interval 32.0 to 54.0	32 percentage of participants Interval 22.0 to 43.0

SECONDARY outcome

Timeframe: Day 57

Population: Per-protocol set included the group of protocol-eligible participants who received 5 days (Cohort 1) or 3 days (Cohort 2) of study treatment and completed at least one scheduled post treatment AK lesion evaluation.

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.

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.
Percentage of Participants With Partial Response of Actinic Keratosis	56 percentage of participants Interval 45.0 to 67.0	52 percentage of participants Interval 41.0 to 63.0

SECONDARY outcome

Timeframe: Baseline, Days 8, 15, 29 and 57

Overall changes from baseline in actinic keratosis lesion counts has been reported.

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.
Overall Change From Baseline in Actinic Keratosis Lesion Counts at Day 8, 15, 29 and 57 Day 8	0.0 lesion count Interval -7.0 to 4.0	-1.0 lesion count Interval -8.0 to 3.0
Overall Change From Baseline in Actinic Keratosis Lesion Counts at Day 8, 15, 29 and 57 Day 15	-2.5 lesion count Interval -8.0 to 5.0	-2.0 lesion count Interval -8.0 to 2.0
Overall Change From Baseline in Actinic Keratosis Lesion Counts at Day 8, 15, 29 and 57 Day 29	-3.0 lesion count Interval -8.0 to 1.0	-4.0 lesion count Interval -8.0 to 2.0
Overall Change From Baseline in Actinic Keratosis Lesion Counts at Day 8, 15, 29 and 57 Day 57	-4.0 lesion count Interval -8.0 to 1.0	-4.0 lesion count Interval -8.0 to 0.0

SECONDARY outcome

Timeframe: Baseline up to Day 57 (Treatment and follow-up period)

Population: Safety analysis set included group of participants who received at least one dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)	34 Participants	18 Participants

SECONDARY outcome

Timeframe: From Day 57 up to 12-months post-Day 57 (Recurrence follow-up period)

Population: Recurrence follow-up set included the group of participants who achieved complete clearance at Day 57.

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.

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=36 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=27 Participants 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.
Number of Participants With Any Treatment-emergent Adverse Events During Recurrence Follow-up Period	5 Participants	3 Participants

SECONDARY outcome

Timeframe: Day 57

Population: Safety analysis set included group of participants who received at least one dose of study treatment.

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).

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Swelling: LSR Grade 3	1 Participants	0 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Swelling: LSR Grade 4	0 Participants	0 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Vesiculation/pustulation: LSR Grade 0	80 Participants	83 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Vesiculation/pustulation: LSR Grade 1	4 Participants	0 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Vesiculation/pustulation: LSR Grade 2	0 Participants	1 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Vesiculation/pustulation: LSR Grade 3	0 Participants	0 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Vesiculation/pustulation: LSR Grade 4	0 Participants	0 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Erosion/ulceration: LSR Grade 0	71 Participants	78 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Erosion/ulceration: LSR Grade 1	12 Participants	6 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Erosion/ulceration: LSR Grade 2	1 Participants	0 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Erosion/ulceration: LSR Grade 3	0 Participants	0 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Erosion/ulceration: LSR Grade 4	0 Participants	0 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Erythema: LSR Grade 0	9 Participants	15 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Erythema: LSR Grade 1	22 Participants	34 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Erythema: LSR Grade 2	35 Participants	29 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Erythema: LSR Grade 3	17 Participants	6 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Erythema: LSR Grade 4	1 Participants	0 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Flaking/Scaling: LSR Grade 0	23 Participants	20 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Flaking/Scaling: LSR Grade 1	20 Participants	33 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Flaking/Scaling: LSR Grade 2	24 Participants	23 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Flaking/Scaling: LSR Grade 3	16 Participants	8 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Flaking/Scaling: LSR Grade 4	1 Participants	0 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Crusting: LSR Grade 0	49 Participants	53 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Crusting: LSR Grade 1	27 Participants	20 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Crusting: LSR Grade 2	8 Participants	10 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Crusting: LSR Grade 3	0 Participants	1 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Crusting: LSR Grade 4	0 Participants	0 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Swelling: LSR Grade 0	66 Participants	76 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Swelling: LSR Grade 1	16 Participants	8 Participants
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs) Swelling: LSR Grade 2	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to Day 57

Population: Safety analysis set included group of participants who received at least one dose of study treatment.

Laboratory parameters included hematology, blood chemistry and urinalysis. Clinical significance was determined by the investigator.

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.
Number of Participants With Clinically Significant Abnormalities in Laboratory	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 57

Population: Safety analysis set included group of participants who received at least one dose of study treatment.

Vital signs included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Clinical significance was determined by the investigator.

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.
Number of Participants With Clinically Significant Abnormalities in Vital Signs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 57

Population: Safety analysis set included group of participants who received at least one dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.
Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs)	4 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 57

Population: Safety analysis set included group of participants who received at least one dose of study treatment.

A physical examination included weight and height measurements was performed. Clinical significance was determined by the investigator.

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.
Number of Participants With Clinically Significant Abnormalities in Physical Examination (PE)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)

Population: Pharmacokinetic (PK) Analysis Set included the group of participants who received study treatment and completed at least one scheduled post-treatment PK evaluation.

Cmax was defined as the maximum observed plasma concentration obtained directly from the concentration versus time curve.

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.
Maximum Observed Plasma Concentration (Cmax) of KX2-391 of KX2-391	NA nanograms/milliliter (ng/mL) Standard Deviation NA Assessments of the PK parameters were planned but were not conducted due to the minimal absorption of KX2-391 in the plasma following 3 or 5 days of consecutive treatment of the 1% ointment. KX2-391 was below the lower limit of quantification (LLOQ) of 0.1 ng/mL for the majority of plasma samples. The maximum individual plasma concentration in both cohorts and all days of PK sampling did not exceed 2 ng/mL.	NA nanograms/milliliter (ng/mL) Standard Deviation NA Assessments of the PK parameters were planned but were not conducted due to the minimal absorption of KX2-391 in the plasma following 3 or 5 days of consecutive treatment of the 1% ointment. KX2-391 was below the lower limit of quantification (LLOQ) of 0.1 ng/mL for the majority of plasma samples. The maximum individual plasma concentration in both cohorts and all days of PK sampling did not exceed 2 ng/mL.

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)

Population: PK Analysis Set included the group of participants who received study treatment and completed at least one scheduled post-treatment PK evaluation.

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.

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.
Area Under the Plasma Concentration Time Curve From Time 0 to the Last Sampling Time (AUCt) of KX2-391	NA nanogramhour per milliliter (ngh/mL) Standard Deviation NA Assessments of the PK parameters were planned but were not conducted due to the minimal absorption of KX2-391 in the plasma following 3 or 5 days of consecutive treatment of the 1% ointment. KX2-391 was below the lower limit of quantification (LLOQ) of 0.1 ng/mL for the majority of plasma samples.	NA nanogramhour per milliliter (ngh/mL) Standard Deviation NA Assessments of the PK parameters were planned but were not conducted due to the minimal absorption of KX2-391 in the plasma following 3 or 5 days of consecutive treatment of the 1% ointment. KX2-391 was below the lower limit of quantification (LLOQ) of 0.1 ng/mL for the majority of plasma samples.

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)

Population: PK Analysis Set included the group of participants who received study treatment and completed at least one scheduled post-treatment PK evaluation.

Cmin was defined as minimum observed plasma concentration obtained directly from the concentration versus time curve.

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.
Minimum Observed Plasma Concentration (Cmin) of KX2-391	NA ng/mL Geometric Coefficient of Variation NA Assessments of the PK parameters were planned but were not conducted due to the minimal absorption of KX2-391 in the plasma following 3 or 5 days of consecutive treatment of the 1% ointment. KX2-391 was below the lower limit of quantification (LLOQ) of 0.1 ng/mL for the majority of plasma samples.	NA ng/mL Geometric Coefficient of Variation NA Assessments of the PK parameters were planned but were not conducted due to the minimal absorption of KX2-391 in the plasma following 3 or 5 days of consecutive treatment of the 1% ointment. KX2-391 was below the lower limit of quantification (LLOQ) of 0.1 ng/mL for the majority of plasma samples.

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)

Population: PK Analysis Set included the group of participants who received study treatment and completed at least one scheduled post-treatment PK evaluation.

Ratio calculated from AUC and Cmax found on the last day of treatment and Day 1.

Outcome measures

Outcome measures
Measure	KX2-391 50 mg (Days 1 to 5) n=84 Participants Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 Participants 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.
Accumulation Ratio (R)	NA ratio Standard Deviation NA Assessments of the PK parameters were planned but were not conducted due to the minimal absorption of KX2-391 in the plasma following 3 or 5 days of consecutive treatment of the 1% ointment. KX2-391 was below the lower limit of quantification (LLOQ) of 0.1 ng/mL for the majority of plasma samples. The maximum individual plasma concentration in both cohorts and all days of PK sampling did not exceed 2 ng/mL.	NA ratio Standard Deviation NA Assessments of the PK parameters were planned but were not conducted due to the minimal absorption of KX2-391 in the plasma following 3 or 5 days of consecutive treatment of the 1% ointment. KX2-391 was below the lower limit of quantification (LLOQ) of 0.1 ng/mL for the majority of plasma samples. The maximum individual plasma concentration in both cohorts and all days of PK sampling did not exceed 2 ng/mL.

Adverse Events

KX2-391 50 mg (Days 1 to 5)

Serious events: 4 serious events

Other events: 37 other events

Deaths: 0 deaths

KX2-391 50 mg (Days 1 to 3)

Serious events: 3 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	KX2-391 50 mg (Days 1 to 5) n=84 participants at risk Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	KX2-391 50 mg (Days 1 to 3) n=84 participants at risk 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.
Cardiac disorders Arteriosclerosis Coronary Artery	0.00% 0/84 • Baseline up to Recurrence Follow-up (12 months post-day 57) Safety analysis set included group of participants who received at least one dose of study treatment.	1.2% 1/84 • Number of events 1 • Baseline up to Recurrence Follow-up (12 months post-day 57) Safety analysis set included group of participants who received at least one dose of study treatment.
Gastrointestinal disorders Small Intestinal Obstruction	1.2% 1/84 • Number of events 1 • Baseline up to Recurrence Follow-up (12 months post-day 57) Safety analysis set included group of participants who received at least one dose of study treatment.	0.00% 0/84 • Baseline up to Recurrence Follow-up (12 months post-day 57) Safety analysis set included group of participants who received at least one dose of study treatment.
Infections and infestations Appendicitis	0.00% 0/84 • Baseline up to Recurrence Follow-up (12 months post-day 57) Safety analysis set included group of participants who received at least one dose of study treatment.	1.2% 1/84 • Number of events 1 • Baseline up to Recurrence Follow-up (12 months post-day 57) Safety analysis set included group of participants who received at least one dose of study treatment.
Nervous system disorders Cerebrovascular Accident	1.2% 1/84 • Number of events 1 • Baseline up to Recurrence Follow-up (12 months post-day 57) Safety analysis set included group of participants who received at least one dose of study treatment.	1.2% 1/84 • Number of events 1 • Baseline up to Recurrence Follow-up (12 months post-day 57) Safety analysis set included group of participants who received at least one dose of study treatment.
Nervous system disorders VIIth Nerve Paralysis	1.2% 1/84 • Number of events 1 • Baseline up to Recurrence Follow-up (12 months post-day 57) Safety analysis set included group of participants who received at least one dose of study treatment.	0.00% 0/84 • Baseline up to Recurrence Follow-up (12 months post-day 57) Safety analysis set included group of participants who received at least one dose of study treatment.
Reproductive system and breast disorders Benign Prostatic Hyperplasia	2.4% 2/84 • Number of events 2 • Baseline up to Recurrence Follow-up (12 months post-day 57) Safety analysis set included group of participants who received at least one dose of study treatment.	0.00% 0/84 • Baseline up to Recurrence Follow-up (12 months post-day 57) Safety analysis set included group of participants who received at least one dose of study treatment.

Other adverse events

Additional Information

Head of Global Clinical Development

Almirall S.A.

Phone: +34932913000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place