Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Multicenter, Randomized, Double-blind, Dose-ranging, Placebo-controlled Study to Evaluate the Efficacy, Response Duration and Safety of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria Who Remain Symptomatic Despite Antihistamine Treatment (H1)
Brief Summary: The study is a global Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of omalizumab administered subcutaneously as an add-on therapy for the treatment of adolescent and adult patients aged 12-75 who have been diagnosed with refractory CIU and who remain symptomatic despite standard-dosed H1 antihistamine treatment.


Options:
A: Inclusion Criteria:

1. Outpatients with moderate to severe CU for more than 6 weeks. Urticaria symptoms must comprise wheal and itch.
2. Patients must exhibit spontaneous urticaria lesions in the randomization visit.
3. History of beneficial effects of antihistaminic treatment.
4. Age between 18 and 60 years.
5. Female patients must be using adequate contraceptive precautions (highly effective method), or they must be postmenopausal, surgically sterilised, or hysterectomised (for details please see protocol).
6. Female patients must be using adequate contraceptive precautions (contraceptive pill, depot, double barrier methods), or they must be postmenopausal, surgically sterilised, or hysterectomised.
7. Voluntarily signed written informed consent.

Exclusion Criteria:

1. The presence of permanent severe diseases, especially those affecting the immune system, except CU.
2. The presence of permanent gastrointestinal condition which may influence the oral therapy (chronic diarrhea diseases, congenital malformations or surgical mutilations of the gastrointestinal tract).
3. History or presence of epilepsy, significant neurological disorders, cerebrovascular attacks or ischemia.
4. History or presence of myocardial infarction or cardiac arrhythmia which requires drug therapy.
5. Evidence of severe renal dysfunction
6. Evidence of significant hepatic disease (liver enzymes twice the upper reference value).
7. The presence of galactose intolerance, lapp lactase deficiency or glucose galactose malabsorption.
8. History of adverse reactions including hypersensitivity to DL and Loratadine.
9. Intake of medicaments that could cause QT changes (drugs listed on www.qtdrugs.org).
10. Presence of active cancer which requires chemotherapy or radiation therapy.
11. Presence of acute urticaria / angioedema including laryngeal edema
12. History or presence of alcohol abuse or drug addiction.
13. Participation in any clinical trial within 4 weeks prior to enrolment.
14. Intake of oral corticosteroids or other immunosuppressive therapy within 14 days prior to the beginning of the study.
15. Use of depot corticosteroids or chronic systemic corticosteroids within 21 days before beginning of the study.
16. Pregnancy or breast-feeding.
17. Existing or planned placement in an institution after ruling according to § 40 passage 1 number 4 AMG (Arzneimittelgesetz).
B: Inclusion Criteria:

* Outpatient, male or female pediatric subject, ages 1 to less than 6 years old at the Randomization Visit (V2) (1 - \< 6 years old)
* The subject must present at least one of the following symptoms, most commonly associated with allergic rhinitis or chronic urticaria: nasal itching, sneezing, rhinorrhea, nasal congestion, tearing, eye redness and itching of eyes, ears and/or palate, skin wheals and itching of the skin
* Subjects (age 2 to less than 6 years only) suffering from allergic rhinitis (AR) should have a documented allergy measured by positive skin prick test or RAST (Radioallergosorbent Test) performed within the last 6 months prior to randomization
* Candidate for antihistamine treatment or received antihistamine in the past for similar symptoms as those presenting
* Caregiver(s) have been informed of the nature and aims of the study and have given their written informed consent for the subject to participate in this study
* Caregiver(s) able to understand information given, the text of the informed consent, and be able to complete the daily record card (DRC)

Exclusion Criteria:

* Any clinically significant medical condition or abnormality other than the primary diagnosis for which an antihistamine is indicated
* Be initiating or changing the dose of an immunotherapy regimen during the course of the study (Visit 1 to Visit 4)
* Any electrocardiogram (ECG) parameters, including a QTcF interval \> 443 msec measured by an ECG obtained at the Screening Visit, outside the normal reference ranges
* Any clinical laboratory tests performed at the Screening Visit, other than those related with the allergic condition, outside the reference ranges. Subjects having values outside the accepted reference range can be included if in the Investigator's opinion, they are of no clinical significance
* Personal history of seizure, febrile seizure or sleep apnea
* Below the lower 5th or above 95th percentile for body weight and/or height based upon CDC Growth Charts for Body Weight and Length
* Allergy or intolerance to levocetirizine dihydrochloride or its excipients, or to any other piperazine derivatives, such as hydroxyzine, cetirizine, cyclizine, meclozine, buclizine
* Current or past intake of the following medications (including exposure through breast milk) within the specified wash-out period before the Randomization Visit (V2):

  1. Systemic corticosteroids within the past 28 days
  2. Leukotriene-receptor antagonists (e.g. montelukast \[Singulair\] or zafirlukast \[Accolate\] within the past 7 days)
  3. Mast-cell stabilizers (e.g. cromolyn or nedocromil) within the past 7 days
  4. Other antihistamines or cough and cold preparations (with the exception of single ingredient guaifenesin products) or over-the-counter (OTC) sleep aid medications within the past 7 days
  5. Systemic antibiotics within the past 7 days
  6. Other concomitant medications that will interfere with the study, in the opinion of the investigator
* Previous participation in another clinical/pharmacological trial within the past month prior to V1
* Have already participated in this study or participated in this study at another site
* Children of any member of the study site staff
C: Inclusion Criteria:

* Outpatient, male or female pediatric subject, aged from 6 to 11 months (6 months - \< 1 year) at the randomization visit
* The subject must present at least one symptom most commonly associated with allergic rhinitis or chronic idiopathic urticaria
* Candidate for antihistamine treatment or received antihistamine in the past for similar symptoms as those presenting

Exclusion Criteria:

* Any clinically significant medical condition or abnormality other than the primary diagnosis for which an antihistamine is indicated
* Be initiating or changing the dose of an immunotherapy regimen during the course of the study (Visit 1 to Visit 4)
* Any Electrocardiogram (ECG) parameters, including a QTcF interval \> 443 msec measured by an ECG obtained at the Screening Visit, outside the normal reference ranges
* Any clinical laboratory tests performed at Screening Visit, other than those related with the allergic condition, outside the reference ranges. Subjects having values outside the accepted reference range can be included if in the Investigator's opinion, they are of no clinical significance
* Personal history of seizure, febrile seizure or sleep apnea
* Below the lower 5th or above 95th percentile for body weight and/or height based upon CDC Growth Charts for Body Weight and Length
* Allergy or intolerance to levocetirizine dihydrochloride or its excipients, or to any other piperazine derivatives, such as hydroxyzine, cetirizine, cyclizine, meclozine, buclizine
* Current or past intake (including exposure through breast milk) of the following medications within the specified wash-out period before the Randomization Visit (V2):

  * Systemic corticosteroids within the past 28 days
  * Leukotriene-receptor antagonists (e.g. montelukast \[Singulair\] or zafirlukast \[Accolate\] within the past 7 days)
  * Mast-cell stabilizers (e.g. cromolyn or nedocromil) within the past 7 days
  * Other antihistamines or cough and cold preparations (with the exception of single ingredient guaifenesin products), or over-the-counter (OTC) sleep aid medications within the past 7 days
  * Systemic antibiotics within the past 7 days
  * Other concomitant medications that will interfere with the study, in the opinion of the investigator
* Previous participation in another clinical/pharmacological trial within the past month prior to V1
* Have already participated in this study or participated in this study at another site
* Children of any member of the study site staff
* Sibling with sleep apnea or sudden infant death syndrome (SIDS)
* Exposure to other conditions known to be potential risk factors for SIDS, such as but not limited to (this should be determined on a case by case basis taking into account the subject's entire medical history and environmental living conditions):

  * Mothers who smoked or abused drugs during pregnancy
  * Extremely young mothers (defined as age 19 or younger when pregnant)
  * Children currently exposed to a caregiver which is a heavy cigarette smoker (defined as smoking at least a pack of cigarettes per day)
  * Babies who sleep regularly on their face or are not put to sleep on their backs
  * Premature birth gestational age ≤ 37 weeks) or low birth weight (below 10 percentile for gestational age)
D: Inclusion Criteria:

* Diagnosis of Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) CIU/CSU refractory to H1 antihistamines at the time of randomization.

Exclusion Criteria:

* Treatment with an investigational agent within 30 days prior to screening.
* Weight \< 20 kg (44 lbs).
* Clearly defined underlying etiology for chronic urticarias other than CIU.
* Evidence of parasitic infection.
* Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or other skin disease associated with itch.
* Previous treatment with omalizumab within a year prior to screening.
* Routine doses of the following medications within 30 days prior to screening: Systemic or cutaneous (topical) corticosteroids (prescription or over the counter), hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide.
* Intravenous (IV) immunoglobulin G (IVIG), or plasmapheresis within 30 days prior to screening.
* Regular (daily/every other day) doxepin (oral) use within 6 weeks prior to screening.
* Any H2 antihistamine use within 7 days prior to screening.
* Any leukotriene receptor antagonist (LTRA) (montelukast or zafirlukast) within 7 days prior to screening.
* Any H1 antihistamines at greater than approved doses within 3 days prior to screening.
* Patients with current malignancy, history of malignancy, or currently under work-up for suspected malignancy except non-melanoma skin cancer that has been treated or excised and is considered resolved.
* Hypersensitivity to omalizumab or any component of the formulation.
* History of anaphylactic shock.
* Presence of clinically significant cardiovascular, neurological, psychiatric, metabolic, or other pathological conditions that could interfere with the interpretation of the study results and or compromise the safety of the patients.
* Evidence of current drug or alcohol abuse.
* Nursing women or women of childbearing potential, unless they meet the following definition of post-menopausal: 12 months of natural amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels \> 40 milli-international units per milliliter (mIU/mL) or 6 weeks post surgical bilateral oophorectomy (with or without hysterectomy) or hysterectomy or are using one or more of the following acceptable methods of contraception: surgical sterilization, hormonal contraception, and double-barrier methods.

Answer: D