Explore the efficacy, safety and tolerability of oral R129160, 60 mg o.d. in patients with chronic idiopathic urticaria
Source
Brief title
Condition
- Angioedema and urticaria
Synonym
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
Reduction of itch after 6 days of treatment
Secondary outcome
• Daily diary evaluation of itch (subject)
• Daily diary evaluation of number of wheals and size largest wheal (subject)
• Daily diary evaluation of interference of skin condition with sleep and
normal daily activities (subject)
• Evaluation of number of wheals and size largest wheal (investigator)
• Evaluation of erythema and skin area involved (investigator)
• Assessment of treatment effectiveness (subject and investigator)
Background summary
Urticaria, also known as nettle rash, is a skin eruption characterized by
wheals (hives) with pale interiors and well-defined red margins and generally
accompanied with an intense itching. Urticaria that appear almost daily or at
least several days a week and that last for at least 6 weeks are called chronic
urticaria. In a substantial fraction of patients with chronic urticaria no
obvious underlying cause for the disease can be identified and the skin
disorder is classified as chronic idiopathic urticaria. In chronic idiopathic
urticaria, intensively itching hives appears daily, or at least several days a
week. Individual hives only last for a few hours, occasionally up to 24 hours.
Histamine plays an important role in the development of the hives. Histamine
dilates the blood vessels (redness) and causes itch.
The mainstay of treatment of chronic idiopathic urticaria is the so-called
antihistamines, medication that inhibit the action of histamine. However, some
of these antihistamines are sedating, and can as such severely impair daytime
activity and alertness. These sedating properties are even more pronounced when
the dosage is increased, a common practice in certain skin disorders
accompanied by intense itching such as chronic idiopathic urticaria.
R129160 is a new antihistamine. In animal models as well as in healthy human
volunteers, the beneficial activity of the compound on histamine-mediated skin
reaction was clearly demonstrated. Furthermore, no sedating effects of the
compound were observed in animal studies or human volunteers, not even with
very high doses (up to 150 mg in human volunteers). In man, R129160 was well
tolerated and no relevant adverse effects were observed. This study is the
first to evaluate the activity of R129160 in chronic idiopathic urticaria.
Study objective
Explore the efficacy, safety and tolerability of oral R129160, 60 mg o.d. in
patients with chronic idiopathic urticaria
Study design
Double-blind, randomized, placebo-controlled, multicentre
Intervention
Form - dosing route : Solution, 12 ml - oral
Investigational drug : R129160 - 60 mg /12 ml solution
Dosage : Total daily dose of 60 mg R129160 once daily
Patients will take one dose of 60 mg in the morning at least 30 minutes before
breakfast.
Duration of treatment : 6 days
Study burden and risks
Although a therapeutic effect is anticipated, we can not promise that your itch
will be significantly alleviated. Furthermore, you can be allocated to the
placebo-group (=study medication without active compound), in which no or only
a minor effect on the itch is expected. Also during the run-in period and the
treatment with placebo, the itch sensation might increase. Furthermore, other
treatments exist for your skin disorder and the associated itch. You can
discuss these alternative options with the study doctor at any time.
Study procedures will not cause any significant pain or discomfort, except
maybe for the discomfort of blood drawing, which may result in a transient
dizziness or weakness, and cause slight discomfort or bruising.
In previous studies a total of 46 patients have been treated with R129160. The
study medication was well tolerated and no major or serious side effects were
reported. However, it is possible that you experience an adverse reaction or
discomfort after the intake of the study medication. The study doctor will
specifically question about any unusual symptom you might have experienced.
België
België
Listed location countries
Age
Inclusion criteria
1. Subjects, male or female, aged between 18 and 65 (extremes included)
2. Confirmed diagnosis of CIU, with history of signs and symptoms for at least 3 days/week during more than 6 consecutive weeks in the 12 months preceding Visit 1, with active disease at the time of inclusion
3. During run-in period (from Visit 1 to Visit 2), pruritus and wheals present for at least 2 days
4. At least moderate pruritus (score of 2 or more) and wheals present (score of 1 or more) during the previous 12 hours
5. Ability to assess their symptom scores accurately and to complete the diary
6. Women of childbearing potential must have a negative urine pregnancy test at screening, must have used a highly effective stable form of birth control (with a failure rate of less than 1%) for at least one month prior to screening and must agree to remain on this effective form of birth control until the first menses after 30 days following the end of study medication treatment. This effective form of birth control consists of oral contraceptives or a contraceptive implant or a depot injection or a contraceptive patch or an IUD.
7. In addition, women of childbearing potential should use a double barrier method (one of the methods mentioned above under item 6 together with a condom and spermicidal agent or a diaphragm and spermicidal agent) from inclusion up to 7 days after end of treatment.
8. Availability of signed informed consent prior to beginning clinical trial protocol-specific procedures, indicating an understanding of the purpose of this trial and a willingness to adhere to the treatment regimen and trial procedures described in this clinical trial protocol
9. In good general health and free of any disease state or physical condition which, in the investigator*s opinion, exposes the subject to an unacceptable risk by trial participation
Exclusion criteria
1. Subjects with urticaria associated with a known underlying disease (eg Hodgkin disease, lupus erythematosus, hepatitis, vasculitis, hyperthyroidism), with physical urticaria (cold, heat, sun-induced, pressure or dermographism, aquagenic), with cholinergic urticaria, with hereditary angioedema or with urticaria due to medications, insect bites, food or any other known etiology
2. Subjects, previously unresponsive to at least two different antihistamines for the treatment of chronic idiopathic urticaria
3. History of drug allergy to antihistamines, other anti-allergic compounds, quinine or any of the components of the trial medication
4. History or suspicion of alcohol and/or drug abuse
5. Subjects having following concomitant disorders: significant hepatic, renal or bone marrow diseases, severe neuropathy including multiple sclerosis, significant psychiatric disorders or any other serious disease (including cancer and subjects known to be HIV positive), significant infection that requires systemic antibiotic treatment
6. Subjects previously randomized in the trial.
7. Any disease state or physical condition that, in the investigator*s opinion, may impair evaluation of itch and/or the urticaria, or may interfere with the treatment
8. Any disease state or surgery known to affect the GI absorption of drugs
9. Out-of-range laboratory test results that the investigator considers as pathologic
10. History of heart failure, myocardial infarction within the past six months, cardiac arrhythmia, or under treatment for heart disorders
11. Clinically significant abnormal ECG-intervals or morphology of the ECG; QT or QTc >470 ms in females or >450 ms in males
12. Use of following medication, unless discontinued at Visit 1: oral and/or topical antihistaminic compounds, including H2 antagonists (exception for Hismanal®: discontinued for at least 4 weeks before Visit 2); topical corticosteroids; topical immuno-modulating agents; other topical and/or systemic anti-allergic or anti-pruritic agents; non steroidal anti-inflammatory drugs (NSAIDs)
13. Use of sedatives or hypnotics within 7 days prior to Visit 1
14. Use of oral corticosteroids; oral immuno-modulating agents; antidepressants, antipsychotics or tranquillizers within 21 days prior to Visit 1
15. Use of intramuscular or intra-articular corticosteroids 90 days prior to Visit 1
16. Pregnant or breastfeeding women, or women of childbearing potential not using adequate contraceptives.
17. Received another investigational drug within the 30 days prior to entry into the trial
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | 2005-002749-38-NL |
CCMO | NL14349.003.06 |