A Multi-Center Study to Evaluate the Efficacy and Safety... | NCT03285490

ID	Type	Description	Link
U1111-1191-8287	Other Identifier	UTN

Name	Class
Athenex, Inc.	INDUSTRY

Label	Type	Description	Intervention Names
KX2-391 Ointment 1%	Experimental	KX2-391 Ointment was applied once daily for 5 consecutive days on the face or scalp.	Drug: KX2-391 Ointment 1%
Placebo	Placebo Comparator	The Vehicle Ointment was applied once daily for 5 consecutive days on the face or scalp.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
KX2-391 Ointment 1%	Drug	Dose: 1% (250 mg single-use packets); Dosage form: Ointment; Route of administration: Topical	KX2-391 Ointment 1%

Measure	Description	Time Frame
Percentage of Participants With Complete (100%) Clearance of Actinic Keratosis (AK) Lesions	Complete clearance rate was defined as the percentage of participants at Day 57 with no clinically visible AK lesions in the treatment area.	Day 57

Measure	Description	Time Frame
Percentage of Participants With Partial Clearance Rate of Actinic Keratosis Lesions at Day 57	Partial clearance rate of AK lesions was defined as the percentage of participants with a greater than or equal to (>=) 75% reduction in the number of AK lesions identified at Baseline (Day 1 predose) in the treatment area.	Day 57

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Males and females greater than or equal to (>=) 18 years old.
A defined area on the face or scalp contains 4 to 8 clinically typical, visible, and discrete AK lesions.
Participants who in the judgment of the Investigator, were in good general health.
Females were postmenopausal (greater than [>] 45 years of age with at least 12 months of amenorrhea), surgically sterile (by hysterectomy, bilateral oophorectomy, or tubal ligation); or, if of childbearing potential, were using highly effective contraception for at least 30 days or 1 menstrual cycle, whichever was longer, prior to study treatment and agreed to continue to use highly effective contraception for at least 30 days following their last dose of study treatment. Highly effective contraception includes oral hormonal contraceptives, hormonal contraceptive implant, injection or patch, intrauterine device or complete abstinence from sexual intercourse.
Sexually active males who had not had a vasectomy, and whose partner was reproductively capable, must had agreed to use barrier contraception from Screening through 90 days after their last dose of study treatment.
All participants must had agreed not to donate sperm or eggs or attempt conception from Screening through 90 days following their last dose of study treatment.
Willing to avoid excessive sun or ultraviolet exposure.
Able to comprehend and were willing to sign the informed consent form (ICF).

Exclusion Criteria

Clinically atypical and/or rapidly changing AK lesions on the treatment area.
Location of the selected area is:
- On any location other than the face or scalp.
- Within 5 centimeters (cm) of an incompletely healed wound.
- Within 5 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC).
Been previously treated with KX2-391 Ointment.
Anticipated need for in-patient hospitalization or in-patient surgery from Day 1 to Day 57.
Treatment with 5-fluorouracil (5-FU), imiquimod, ingenol mebutate, diclofenac, photodynamic therapy, or other treatments for AK within the treatment area or within 2 cm of the treatment area, within 8 weeks prior to the Screening visit.
Use of the following therapies and/or medications within 2 weeks prior to the Screening visit:
- Cosmetic or therapeutic procedures (e.g., use of liquid nitrogen, surgical excision, curettage, dermabrasion, medium or greater depth chemical peel, laser resurfacing) within the treatment area or within 2 cm of the selected treatment area.
- Acid-containing therapeutic products (eg, salicylic acid or fruit acids, such as alpha- and beta-hydroxyl acids and glycolic acids), topical retinoids, or light chemical peels within the treatment area or within 2 cm of the selected treatment area.
- Topical salves (non-medicated/non-irritant lotion and cream were acceptable) or topical steroids within the treatment area or within 2 cm of the selected treatment area; artificial tanners within the treatment area or within 5 cm of the selected treatment area.
Use of the following therapies and/or medications within 4 weeks prior to the Screening visit:
- Treatment with immunomodulators (eg, azathioprine), cytotoxic drugs (eg, cyclophosphamide, vinblastine, chlorambucil, methotrexate) or interferons/interferon inducers.
- Treatment with systemic medications that suppress the immune system (eg, cyclosporine, prednisone, methotrexate, alefacept, infliximab).
Use of systemic retinoids (eg, isotretinoin, acitretin, bexarotene) within 6 months prior to the Screening visit.
A history of sensitivity and/or allergy to any of the ingredients in the study medication.
A skin disease (e.g., atopic dermatitis, psoriasis, eczema) or condition (e.g., scarring, open wounds) that, in the opinion of the Investigator, might interfere with the study conduct or evaluations, or which exposes the participant to 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 were pregnant or nursing.
Participated in an investigational drug trial during which an investigational study medication was administered within 30 days or 5 half-lives of the investigational product, whichever was longer, before dosing.

Name	Affiliation	Role
Jane Fang, MD	Athenex, Inc.	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Alliance Dermatology		Phoenix	Arizona	85032	United States
Synexus US

PubMed Identifier	Type	Citation	Retractions
33567191	Derived	Blauvelt A, Kempers S, Lain E, Schlesinger T, Tyring S, Forman S, Ablon G, Martin G, Wang H, Cutler DL, Fang J, Kwan MR; Phase 3 Tirbanibulin for Actinic Keratosis Group. Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis. N Engl J Med. 2021 Feb 11;384(6):512-520. doi: 10.1056/NEJMoa2024040.

ID	Title	Description
FG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 centimeter square (cm^2) on face or scalp.
FG001	KX2-391 Ointment 1%

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 18, 2018	Feb 2, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Complete (100%) Clearance of Actinic Keratosis (AK) Lesions

Complete clearance rate was defined as the percentage of participants at Day 57 with no clinically visible AK lesions in the treatment area.

ITT population included all randomized participants.

Posted

Number

percentage of participants

Day 57

ID	Title	Description
OG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.
OG001	KX2-391 Ointment 1%	KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.

Units	Counts
Participants	OG000173 OG001178

Title

Denominators

Categories

Title	Measurements
	OG00013 OG00154

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Statistical significance in the study for Day 57 complete clearance rate was analyzed using a Cochran-Mantel-Haenszel model controlling for treatment location (face or scalp) and treatment group (Placebo versus KX2-391 Ointment 1%).	Cochran-Mantel-Haenszel		<0.0001	P-value threshold for statistical significance was 0.5%													Superiority

Secondary

Percentage of Participants With Partial Clearance Rate of Actinic Keratosis Lesions at Day 57

Partial clearance rate of AK lesions was defined as the percentage of participants with a greater than or equal to (>=) 75% reduction in the number of AK lesions identified at Baseline (Day 1 predose) in the treatment area.

ITT population included all randomized participants.

Posted

Number

percentage of participants

Day 57

ID	Title	Description
OG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.
OG001	KX2-391 Ointment 1%	KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.

Units	Counts
Participants	OG000

Secondary

Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57

Overall the change from baseline in lesion count at each visit were summarized and reported using descriptive statistics by treatment location (face or scalp).

ITT population included all randomized participants.

Posted

Median

Full Range

lesion count

Days 8, 15, 29 and 57

ID	Title	Description
OG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.
OG001	KX2-391 Ointment 1%	KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57

Recurrence rate was estimated based on Kaplan-Meier method, with recurrence define as appearance of any AK lesions in the treatment area, including those recurred or newly identified.

Recurrence follow-up population included all participants in the ITT Population who achieved complete clearance at the Day 57 visit. The recurrence rate was evaluated only for KX2-391 Ointment 1% arm, pre-specified in protocol.

Posted

Number

percentage of participants

3, 6, 9 and 12 months post-Day 57

ID	Title	Description
OG000	KX2-391 Ointment 1%	KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR)

Maximal post baseline LSR was defined as the highest grade of any LSR reported at any post baseline visits for a participant. The LSR assessment was an Investigator's (or sub-investigator's) assessment of the following signs on the treatment area: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. The LSRs were graded on a 4-point scale ranging from 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense).

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

Posted

Count of Participants

Participants

Day 57

ID	Title	Description
OG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.
OG001	KX2-391 Ointment 1%	KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.

Units	Counts
Participants

Secondary

Number of Participants With Pigmentation and Scarring in the Treatment Area

Absence or presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment area were assessed.

Safety Population included all randomized participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

Baseline (Day 1 predose), Days 5, 8, 15, 29 and 57

ID	Title	Description
OG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.
OG001	KX2-391 Ointment 1%	KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests

An AE was defined as any untoward medical occurrence in participant which does not necessarily have causal relationship with treatment. An AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal product, whether or not considered related to medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. TEAEs (serious and non-serious) were defined as either those AEs with onset after first dose or those pre-existing AEs that worsen after first dose. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.

Safety Population included all randomized participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

Baseline (Day 1 predose) up to Day 57

ID	Title	Description
OG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.
OG001	KX2-391 Ointment 1%

Secondary

Number of Participants With Adverse Events, Serious Adverse Events, Events of Special Interests Within the Treatment Area After Day 57 and up to 12 Months Post-Day 57

An AE was defined as any untoward medical occurrence in participant which does not necessarily have causal relationship with treatment. An AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal product, whether or not considered related to medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.

Recurrence follow-up population included all participants in the ITT Population who achieved complete clearance at the Day 57 visit.

Posted

Count of Participants

Participants

From Day 57 up to 12-months post-Day 57

ID	Title	Description
OG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.
OG001	KX2-391 Ointment 1%	KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.

Secondary

Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis

Assessed laboratory parameters included hematology, blood chemistry and urinalysis. Clinical significance and abnormal observations were determined by the investigator.

Safety Population included all randomized participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

From Baseline (Day 1 predose) up to Day 57

ID	Title	Description
OG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.
OG001	KX2-391 Ointment 1%	KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Clinically Significant Safety Observations- Vital Signs

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

Safety Population included all randomized participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

From Baseline (Day 1 predose) up to Day 57

ID	Title	Description
OG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.
OG001	KX2-391 Ointment 1%	KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Clinically Significant Safety Observations- Physical Examination

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

Safety Population included all randomized participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

From Baseline (Day 1 predose) up to Day 57

ID	Title	Description
OG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.
OG001	KX2-391 Ointment 1%	KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Clinically Significant Safety Observations- Electrocardiograms (ECGs)

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.

Safety Population included all randomized participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

From Baseline (Day 1 predose) up to Day 57

ID	Title	Description
OG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.
OG001	KX2-391 Ointment 1%	KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Arrhythmia	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Atrial flutter	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Tachycardia	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Diplopia	Eye disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0011 events1 affected178 at risk
Bowel movement irregularity	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Food poisoning	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Application site pruritus	General disorders	MedDRA 20.0	Non-systematic Assessment	EG00013 events13 affected173 at risk EG00119 events19 affected178 at risk
Application site pain	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0005 events5 affected173 at risk EG00131 events24 affected178 at risk
Application site inflammation	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Application site nodule	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Application site paraesthesia	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Application site scab	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Chest discomfort	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Influenza like illness	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Nodule	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Non-cardiac chest pain	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Peripheral swelling	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Seasonal allergy	Immune system disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG00010 events10 affected173 at risk EG0018 events8 affected178 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0004 events4 affected173 at risk EG0019 events9 affected178 at risk
Cellulitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0012 events2 affected178 at risk
Sinusitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected173 at risk EG0010 events0 affected178 at risk
Urinary tract infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected173 at risk EG0011 events1 affected178 at risk
Influenza	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected173 at risk EG0011 events1 affected178 at risk
Angular cheilitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Application site folliculitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Bronchitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0011 events1 affected178 at risk
Carbuncle	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Herpes simplex	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Labyrinthitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected173 at risk EG0010 events0 affected178 at risk
Localised infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Onychomycosis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Post procedural infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Postoperative wound infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Pyuria	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Streptococcal infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Tooth infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0004 events3 affected173 at risk EG0014 events4 affected178 at risk
Animal bite	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected173 at risk EG0011 events1 affected178 at risk
Face injury	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0012 events1 affected178 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Tooth fracture	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected173 at risk EG0010 events0 affected178 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Blood testosterone decreased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Cardiac murmur	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Crystal urine present	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Prostatic specific antigen increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Urobilinogen urine increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Haemochromatosis	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0012 events2 affected178 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0012 events2 affected178 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0005 events4 affected173 at risk EG0013 events3 affected178 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected173 at risk EG0014 events3 affected178 at risk
Haemangioma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Malignant melanoma in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Melanocytic naevus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Renal cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Seborrhoeic keratosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Squamous cell carcinoma of head and neck	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected173 at risk EG0010 events0 affected178 at risk
Headache	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected173 at risk EG0011 events1 affected178 at risk
Dysgeusia	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Nervous system disorder	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Ketonuria	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected173 at risk EG0011 events1 affected178 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected173 at risk EG0010 events0 affected178 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0011 events1 affected178 at risk
Actinic keratosis	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0015 events2 affected178 at risk
Blister	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0012 events2 affected178 at risk
Lentigo	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Rosacea	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Scab	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0011 events1 affected178 at risk
Skin tightness	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Arthrodesis	Surgical and medical procedures	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Hypertension	Vascular disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0011 events1 affected178 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Tongue disorder	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Bacteriuria	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Dizziness	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk
Glycosuria	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Proteinuria	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected173 at risk EG0011 events1 affected178 at risk
Meniscus operation	Surgical and medical procedures	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected173 at risk EG0010 events0 affected178 at risk

ID	Term
D055623	Keratosis, Actinic
D007642	Keratosis
D011230	Precancerous Conditions
D009369	Neoplasms

ID	Term
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Title	Description
BG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.
BG001	KX2-391 Ointment 1%	KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.	0	173	4	173	72	173
EG001	KX2-391 Ointment 1%	KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 on face or scalp.	0	178	1	178	72	178