ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials
of another drug and may not reflect the rates observed in clinical practice.
The data described below reflect exposure to Picato® gel in 499 subjects with actinic keratosis,
including 274 subjects exposed to Picato® gel field treatment (skin area of 25 cm2 in the face or
scalp regions) at a concentration of 0.015% once daily for 3 consecutive days, and 225 subjects
exposed to Picato® gel field treatment (skin area of 25 cm2 in the trunk or extremities regions) at
a concentration of 0.05% once daily for 2 consecutive days.
Local skin reactions, including erythema, flaking/scaling, crusting, swelling,
vesiculation/pustulation, and erosion/ulceration were assessed within the selected treatment area
and graded by the investigator on a scale of 0 to 4. A grade of 0 represented no reaction present
in the treated area, and a grade of 4 indicated a marked and severe skin reaction that extended
beyond the treated area.
Table 1 Investigator Assessment of Maximal Local Skin Reactions in the Treatment Area during the 57 Days Post Treatment Period (face/scalp trials)
Face and Scalp
(n=545)
Picato® gel, 0.015% once daily for 3 days
|
Skin reactions
|
Any Gradea > Baseline
|
Grade 4
|
|
Picato® gel
(n=274)
|
Vehicle
(n=271)
|
Picato® gel
(n=274)
|
Vehicle
(n=271)
|
Erythema
|
258 (94%)
|
69 (25%)
|
66 (24%)
|
0 (0%)
|
Flaking/Scaling
|
233 (85%)
|
67 (25%)
|
25 (9%)
|
0 (0%)
|
Crusting
|
220 (80%)
|
46 (17%)
|
16 (6%)
|
0 (0%)
|
Swelling
|
217 (79%)
|
11 (4%)
|
14 (5%)
|
0 (0%)
|
Vesiculation/Pustulation
|
154 (56%)
|
1 (0%)
|
15 (5%)
|
0 (0%)
|
Erosion/Ulceration
|
87 (32%)
|
3 (1%)
|
1 (0%)
|
0 (0%)
|
aMild (grade 1), Moderate (grade 2-3) or Severe (grade 4).
Table 2 Investigator Assessment of Maximal Local Skin Reactions in the Treatment Area during the 57 Days Post Treatment Period (trunk/extremities trials)
Trunk and Extremities
(n=457)
Picato® gel, 0.05% once daily for 2 days
|
Skin reactions
|
Any Gradea > Baseline
|
Grade 4
|
|
Picato® gel
(n=225)
|
Vehicle
(n=232)
|
Picato® gel
(n=225)
|
Vehicle
(n=232)
|
Erythema
|
207 (92%)
|
43 (19%)
|
34 (15%)
|
0 (0%)
|
Flaking/Scaling
|
203 (90%)
|
44 (19%)
|
18 (8%)
|
0 (0%)
|
Crusting
|
167 (74%)
|
23 (10%)
|
8 (4%)
|
0 (0%)
|
Swelling
|
143 (64%)
|
13 (6%)
|
7 (3%)
|
0 (0%)
|
Vesiculation/Pustulation
|
98 (44%)
|
2 (1%)
|
3 (1%)
|
0 (0%)
|
Erosion/Ulceration
|
58 (26%)
|
6 (3%)
|
2 (1%)
|
0 (0%)
|
aMild (grade 1), Moderate (grade 2-3) or Severe (grade 4).
Local skin reactions typically occurred within 1 day of treatment initiation, peaked in intensity
up to 1 week following completion of treatment, and resolved within 2 weeks for areas treated on
the face and scalp, and within 4 weeks for areas treated on the trunk and extremities.
Adverse reactions that occurred in
≥
2% of subjects treated with Picato® gel and at a higher
frequency than the vehicle are presented in Table 3 and Table 4.
Table 3 Adverse reactions occurring in ≥ 2% of subjects treated with Picato® gel and at higher frequency than vehicle (face/scalp trials)
|
Face/Scalp
|
Adverse Reactions
|
Picato® gel, 0.015%
(N=274)
|
Vehicle
(N=271)
|
Application Site Pain
|
42 (15%)
|
1 (0%)
|
Application Site Pruritus
|
22 (8%)
|
3 (1%)
|
Application Site Infection
|
7 (3%)
|
0 (0%)
|
Periorbital Edema
|
7 (3%)
|
0 (0%)
|
Headache
|
6 (2%)
|
3 (1%)
|
Table 4 Adverse reactions occurring in ≥ 2% of subjects treated with Picato® gel and at higher frequency than vehicle (trunk/extremities trials)
|
Trunk/Extremities
|
Adverse Reactions
|
Picato® gel, 0.05%
(N=225)
|
Vehicle
(N=232)
|
Application Site Pruritus
|
18 (8%)
|
0 (0%)
|
Application Site Irritation
|
8 (4%)
|
1 (0%)
|
Nasopharyngitis
|
4 (2%)
|
2 (1%)
|
Application Site Pain
|
5 (2%)
|
0 (0%)
|
Less common adverse reactions in subjects treated with Picato® included: eyelid edema, eye
pain, conjunctivitis.
A total of 108 subjects treated with Picato® gel on the face/scalp and 38 subjects treated on the trunk/extremities were followed for 12 months. Results from these studies did not change the safety profile of Picato® gel.
|