Trial Outcomes & Findings for A Study of Equivalence of Generic Ingenol Mebutate Gel 0.05% and Picato Gel 0.05% in Subjects With Actinic Keratosis (NCT NCT02654769)

Last Updated: 2020-05-12

Results Overview

Percentage of subjects in the PP population in each treatment group with complete clearance of AK lesions. Complete clearance was defined as having no (zero) clinically visible AK lesions in the Treatment Area at the Week 8 visit.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

441 participants

Primary outcome timeframe

8 weeks

Results posted on

2020-05-12

Participant Flow

Participant milestones

Participant milestones
Measure	Active Comparator Picato® Picato® (ingenol mebutate) gel, 0.05% (Leo Pharma Inc.) \[Reference Listed Drug (RLD)\] Ingenol Mebutate (Picato®): Brand product	Generic Ingenol Mebutate Generic ingenol mebutate gel, 0.05% \[Test\] Generic Ingenol Mebutate: Generic formulated to have the same therapeutic effect of the brand	Vehicle Foam Vehicle gel of the test product Vehicle Foam: It does not contain active ingredient. A placebo to test the sensitivity of the active treatments.
Overall Study STARTED	149	149	143
Overall Study COMPLETED	145	148	142
Overall Study NOT COMPLETED	4	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Equivalence of Generic Ingenol Mebutate Gel 0.05% and Picato Gel 0.05% in Subjects With Actinic Keratosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Comparator Picato® n=148 Participants Picato® (ingenol mebutate) gel, 0.05% (Leo Pharma Inc.) \[Reference Listed Drug (RLD)\] Ingenol Mebutate (Picato®): Brand product	Generic Ingenol Mebutate n=149 Participants Generic ingenol mebutate gel, 0.05% \[Test\] Generic Ingenol Mebutate: Generic formulated to have the same therapeutic effect of the brand	Vehicle Foam n=142 Participants Vehicle gel of the test product Vehicle Foam: It does not contain active ingredient. A placebo to test the sensitivity of the active treatments.	Total n=439 Participants Total of all reporting groups
Age, Continuous	67.4 years STANDARD_DEVIATION 9.49 • n=5 Participants	66.6 years STANDARD_DEVIATION 11.11 • n=7 Participants	66.2 years STANDARD_DEVIATION 9.07 • n=5 Participants	66.7 years STANDARD_DEVIATION 9.93 • n=4 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	76 Participants n=7 Participants	66 Participants n=5 Participants	200 Participants n=4 Participants
Sex: Female, Male Male	90 Participants n=5 Participants	73 Participants n=7 Participants	76 Participants n=5 Participants	239 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	12 Participants n=7 Participants	13 Participants n=5 Participants	40 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	133 Participants n=5 Participants	137 Participants n=7 Participants	129 Participants n=5 Participants	399 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	148 Participants n=5 Participants	149 Participants n=7 Participants	141 Participants n=5 Participants	438 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Fitzpatrick Skin Type I	26 Participants n=5 Participants	32 Participants n=7 Participants	22 Participants n=5 Participants	80 Participants n=4 Participants
Fitzpatrick Skin Type II	63 Participants n=5 Participants	56 Participants n=7 Participants	67 Participants n=5 Participants	186 Participants n=4 Participants
Fitzpatrick Skin Type III	49 Participants n=5 Participants	52 Participants n=7 Participants	43 Participants n=5 Participants	144 Participants n=4 Participants
Fitzpatrick Skin Type IV	9 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants	27 Participants n=4 Participants
Fitzpatrick Skin Type V	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: Per-Protocol Population

Outcome measures

Outcome measures
Measure	Active Comparator Picato® n=131 Participants Picato® (ingenol mebutate) gel, 0.05% (Leo Pharma Inc.) \[Reference Listed Drug (RLD)\] Ingenol Mebutate (Picato®): Brand product	Generic Ingenol Mebutate n=135 Participants Generic ingenol mebutate gel, 0.05% \[Test\] Generic Ingenol Mebutate: Generic formulated to have the same therapeutic effect of the brand	Vehicle Foam n=132 Participants Vehicle gel of the test product Vehicle Foam: It does not contain active ingredient. A placebo to test the sensitivity of the active treatments.
Primary Efficacy Outcome Measure	50 Participants	49 Participants	8 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Per-Protocol Population

Outcome measures

Outcome measures
Measure	Active Comparator Picato® n=131 Participants Picato® (ingenol mebutate) gel, 0.05% (Leo Pharma Inc.) \[Reference Listed Drug (RLD)\] Ingenol Mebutate (Picato®): Brand product	Generic Ingenol Mebutate n=135 Participants Generic ingenol mebutate gel, 0.05% \[Test\] Generic Ingenol Mebutate: Generic formulated to have the same therapeutic effect of the brand	Vehicle Foam n=132 Participants Vehicle gel of the test product Vehicle Foam: It does not contain active ingredient. A placebo to test the sensitivity of the active treatments.
The Percentage of Subjects in the PP Population in Each Treatment Group With Partial Clearance (as Having at Least 75% Reduction in the Number of Clinically Visible AK Lesions) in theTreatment Area at the Week 8 Visit.	84 Participants	83 Participants	21 Participants

Adverse Events

Generic Ingenol Mebutate

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Active Comparator Picato®

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Vehicle Foam

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Senior Director, Clinical R&D

Teva Pharmaceuticals Inc., USA

Phone: 1-888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The results of the study may be published or presented by the Investigator(s) after the review by, and in consultation and agreement with the Sponsor, and such that confidential or proprietary information is not disclosed.
Publication restrictions are in place

Restriction type: OTHER

Measure	Generic Ingenol Mebutate n=149 participants at risk Generic ingenol mebutate gel, 0.05% \[Test\] Generic Ingenol Mebutate: Generic formulated to have the same therapeutic effect of the brand	Active Comparator Picato® n=149 participants at risk Picato® (ingenol mebutate) gel, 0.05% (Leo Pharma Inc.) \[Reference Listed Drug (RLD)\] Ingenol Mebutate (Picato®): Brand product	Vehicle Foam n=143 participants at risk Vehicle gel of the test product Vehicle Foam: It does not contain active ingredient. A placebo to test the sensitivity of the active treatments.
Cardiac disorders Angina pectoris	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Cardiac disorders Coronary artery disease	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Ear and labyrinth disorders Hypoacusis	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Ear and labyrinth disorders Tinnitus	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Ear and labyrinth disorders Vertigo	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Endocrine disorders Hypothyroidism	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Eye disorders Conjunctival irritation	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Eye disorders Erythema of eyelid	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Eye disorders Eyelid oedema	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Gastrointestinal disorders Dry mouth	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Gastrointestinal disorders Gastrointestinal wall thickening	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Gastrointestinal disorders Inguinal hernia	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Gastrointestinal disorders Large intestine perforation	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Gastrointestinal disorders Nausea	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Gastrointestinal disorders Toothache	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
General disorders Application site erosion	1.3% 2/149 • From the start of the study until Week 8 (end of study).	1.3% 2/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
General disorders Application site hypoaesthesia	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
General disorders Application site pain	0.00% 0/149 • From the start of the study until Week 8 (end of study).	4.7% 7/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
General disorders Application site pruritus	0.67% 1/149 • From the start of the study until Week 8 (end of study).	2.0% 3/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
General disorders Application site scab	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
General disorders Application site vesicles	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
General disorders Death	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Infections and infestations Application site abscess	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Infections and infestations Application site cellulitis	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Infections and infestations Gastroenteritis viral	0.00% 0/149 • From the start of the study until Week 8 (end of study).	1.3% 2/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Infections and infestations Genital herpes simplex	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Infections and infestations Nasopharyngitis	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Infections and infestations Sinusitis	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Infections and infestations Staphyloccocall skin infection	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Infections and infestations Upper respiratory tract infection	0.00% 0/149 • From the start of the study until Week 8 (end of study).	1.3% 2/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Injury, poisoning and procedural complications Joint injury	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Injury, poisoning and procedural complications Laceration	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Injury, poisoning and procedural complications Muscle strain	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	2.1% 3/143 • From the start of the study until Week 8 (end of study).
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Injury, poisoning and procedural complications Wound	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Investigations Blood triglycerides increased	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Metabolism and nutrition disorders Hyperlipidaemis	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Metabolism and nutrition disorders Vitamin D deficiency	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Musculoskeletal and connective tissue disorders Arthralgia	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of skin	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of skin	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Nervous system disorders Headache	1.3% 2/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Nervous system disorders Occipital neuralgia	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Nervous system disorders Sciatica	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Nervous system disorders Syncope	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Psychiatric disorders Insomnia	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Renal and urinary disorders Pollakiuria	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Respiratory, thoracic and mediastinal disorders Cough	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Respiratory, thoracic and mediastinal disorders Wheezing	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/149 • From the start of the study until Week 8 (end of study).	1.3% 2/149 • From the start of the study until Week 8 (end of study).	0.70% 1/143 • From the start of the study until Week 8 (end of study).
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Skin and subcutaneous tissue disorders Photodermatosis	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Skin and subcutaneous tissue disorders Rash	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).
Vascular disorders Spider vein	0.00% 0/149 • From the start of the study until Week 8 (end of study).	0.67% 1/149 • From the start of the study until Week 8 (end of study).	0.00% 0/143 • From the start of the study until Week 8 (end of study).