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.
In four double-blind, placebo-controlled, randomized
clinical studies, a total of 1279 subjects with house dust mite-induced
allergic rhinitis, with or without conjunctivitis, 18 through 65 years of age
was treated with at least one dose of ODACTRA 12 SQ-HDM. Of subjects treated
with ODACTRA in the four studies, 50% had mild to moderate asthma and 71% were
polysensitized to other allergens in addition to HDM, including trees, grasses,
weeds, molds, and animal danders. The study population was 88% White, 6%
African American, 4% Asian and 55% female.
Study 1 (NCT01700192) was a randomized, double-blind,
placebo-controlled study conducted in the US and Canada evaluating ODACTRA in
1482 subjects 12 years of age and older with house dust miteinduced allergic
rhinitis with or without conjunctivitis. Of the 1482 subjects, 640 subjects 18
through 65 years of age received at least one dose of ODACTRA, with a median
treatment duration of 267 days (range 1 to 368 days). 631 subjects received
placebo. Placebo tablets contained the same inactive ingredients as ODACTRA
without allergen extract and were packaged identically so that treatment
blind/masking was maintained. Participants were monitored for unsolicited
adverse events and serious adverse events (SAEs) for the duration of therapy
(up to 52 weeks). Participants were monitored for solicited adverse reactions
for the first 28 days following treatment initiation.
Study participants were provided side effect report cards
in which they recorded the occurrence of specific solicited adverse reactions
daily for the first 28 days following treatment initiation with ODACTRA or
placebo. In Study 1, the most common solicited adverse reactions reported in ≥10%
of subjects treated with ODACTRA were: throat irritation/tickle (67.0% vs.
20.8% placebo), itching in the mouth (61.3% vs. 14.1%), itching in the ear
(51.7% vs. 11.7%), swelling of the uvula/back of the mouth (19.8% vs. 2.4%), swelling
of the lips (18.0% vs. 2.7%), swelling of the tongue (15.8% vs. 2.1%), nausea
(14.2% vs. 7.1%), tongue pain (14.2% vs. 3.0%), throat swelling (13.6% vs.
2.4%), tongue ulcer/sore on the tongue (11.6% vs. 2.1%), stomach pain (11.3%
vs. 5.2%), mouth ulcer/sore in the mouth (10.3% vs. 2.9%), and taste alteration/food
tastes different (10.0% vs. 3.6%). Table 1 summarizes all solicited adverse
reactions reported within the first 28 days of treatment initiation in subjects
18 through 65 years of age using the patient-friendly term.
Table 1: Percentages of Solicited* Adverse Reactions
Within 28 Days After Initiation of Treatment with ODACTRA (Study 1, Safety
Analysis Set) in Patients 18 through 65 Years of Age (NCT01700192)
|Adverse Reaction (Patient-Friendly Term)
||Study Population: Study 1 Adverse Reactions of Any Intensity
||Study Population: Study 1 Adverse Reactions That Were Severe†
|Ear and labyrinth disorders
|Itching in the ear
|Itching in the mouth
|Swelling of the uvula/back of the mouth‡
|Swelling of the lips
|Swelling of the tongue
|Tongue ulcer/sore on the tongue
|Mouth ulcer/sore in the mouth
|Nervous system disorders
|Taste alteration/food tastes different
|Respiratory, thoracic and mediastinal disorders
|In Table 1, the dashes represent no subjects.
*Solicited adverse reactions (modified from World Allergy Organization [WAO]
list of local side effects of sublingual immunotherapy [SLIT]) were those
reported by subjects within the first 28 days after treatment initiation.
†Severe adverse reactions were those assessed by the investigator as severe in
intensity, which is defined as incapacitating with inability to work or do
‡The percentage of subjects reported for the patient-friendly term of
“swelling of the uvula/back of the mouth” includes subjects with an
enlarged uvula, palatal swelling/edema, and/or mouth swelling/edema (which can
be anywhere in the mouth, not specifically back of the mouth).
In Study 1, the timing of the adverse reaction relative
to exposure to ODACTRA was evaluated for 7 solicited adverse reactions (itching
in the ear, itching in the mouth, swelling of the uvula/back of the mouth, swelling
of the lips, swelling of the tongue, throat irritation/tickle, and throat
swelling). The median time to onset of these adverse reactions following
initiation of treatment with ODACTRA varied from 1 to 7 days. The median
duration of these adverse reactions that occurred on the first day of treatment
initiation varied from 30 to 60 minutes. These adverse reactions recurred for a
median of 2 to 12 days.
In Study 1, the following unsolicited adverse events were
reported in numerically more subjects treated with ODACTRA than with placebo
and occurred in ≥1% of subjects 18 through 65 years of age within 28 days
after initiation of treatment with ODACTRA: paresthesia oral (9.2% vs. 3.2%),
tongue pruritus (4.7% vs. 1.1%), oral pain (2.7% vs. 0.6%), stomatitis (2.5%
vs. 1.1%), dyspepsia (2.2% vs. 0.0%), pharyngeal erythema (2.0% vs. 0.3%), eye
pruritus (1.7% vs. 1.4%), oral mucosal erythema (1.7% vs. 0.2%), upper
respiratory tract infection (1.6% vs. 1.1%), sneezing (1.6% vs. 0.3%), lip
pruritus (1.4% vs. 0.3%), dysphagia (1.4% vs. 0.0%), fatigue (1.3% vs. 1.0%),
hypoesthesia oral (1.3% vs. 1.0%), oropharyngeal pain (1.3% vs. 0.6%), chest
discomfort (1.3% vs. 0.3%), dry throat (1.3% vs. 0.3%), pruritus (1.1% vs.
1.0%), and urticaria (1.1% vs. 0.3%).
Studies 2 (NCT01454544) and 3 (NCT01644617) were
randomized, double-blind, placebo-controlled studies of subjects 18 years of
age and older with house dust mite-induced allergic rhinitis with or without conjunctivitis,
and with or without asthma. Study 4 (NCT01433523) was a randomized,
double-blind placebo-controlled study that included subjects 18 years of age
and older with house dust mite-induced asthma and allergic rhinitis, with or
Across the four clinical studies, 1279 subjects received
at least one dose of ODACTRA, of whom 1104 (86%) completed at least 4 months of
The percentages of subjects in these studies who
discontinued treatment because of an adverse reaction while exposed to ODACTRA
or placebo were 8.1% and 3.0%, respectively. The most common adverse reactions
(≥1.0%) that led to study discontinuation in subjects who received
ODACTRA were throat irritation (1.5%), oral pruritus (1.3%), ear pruritus
(1.1%), and mouth swelling (1.0%).
Serious adverse events were reported, 16/1279 (1.3%)
among ODACTRA recipients and 23/1277 (1.8%) among placebo recipients. No deaths
Epinephrine use was reported in 5/1279 (0.4%) subjects
who received ODACTRA compared to 3/1277 (0.2%) of subjects who received
placebo. Of these subjects, 1 ODACTRA recipient reported a systemic allergic
reaction and used epinephrine on the day of treatment initiation compared to 2
placebo recipients who reported anaphylaxis and used epinephrine 6 and 25 days
after treatment initiation, respectively.
Of 1279 subjects who received ODACTRA, 34 (2.7%) reported
dyspepsia compared to 0/1277 (0%) of subjects who received placebo. Twenty
subjects who received ODACTRA (1.6%) reported symptoms of gastroesophageal
reflux disease (GERD) compared to 3/1277 (0.2%) of subjects who received
Across 8 clinical studies conducted with different doses
of ODACTRA, eosinophilic esophagitis was reported in 2/2737 (0.07%) subjects
who received ODACTRA compared to 0/1636 (0%) subjects who received placebo.
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