A 2 week multiple ascending dose, double-blind placebo controlled study to evaluate the safety, tolerability and pharmacokinetics (PK) of twice daily administration of oral AEB071 and to explore the pharmacodynamics (PD) of oral AEB071 in moderate to severe psoriasis patients.
- Conditions
- moderate to severe chronic plaque psoriasis patientsMedDRA version: M15Level: LLTClassification code 10050576
- Registration Number
- EUCTR2004-003972-12-GB
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 24
1. Male or female patients from 18-65 years of age and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
2. Female patients must be postmenopausal (i.e. must have had no regular menstrual bleeding for at least 2 years prior to inclusion) or must have been surgically sterilized (bilateral oophorectomy) or hysterectomized at least 6 months prior to screening. Menopause will be confirmed by a plasma 17ß-estradiol concentration of <20 pg/mL and a plasma FSH level of >40 IU/L. Surgical sterilization procedures or hysterectomy must be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF
3. Body weight must be between 50 and 100kg (inclusive).
4. Moderate/severe chronic plaque psoriasis.
5. Able to provide written informed consent prior to study participation.
Subject information and consent forms generated by the investigator must be approved by the sponsor prior to submission to the Ethics Committee (EC)/Institutional Review Board (IRB). A copy of the subject information and consent forms approved by the EC/IRB must be forwarded to the sponsor prior to study initiation.
6. Able to communicate well with the investigator and comply with the requirements of the study.
Additional criteria for cohort 4:
Male patients must agree to use double barrier methods of contraception (condoms and spermicide) for the duration of the study and until one month after receiving the last dose of study medication. Also, male patients should not donate sperm for the duration of the study until one month after receiving the last dose of study medication.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Use of any prescription drug or over-the-counter (OTC) medication (including herbal remedies) within 2 weeks prior to dosing. Paracetamol is acceptable, but must be documented in the Concomitant medications / Significant non-drug therapies page of the eCRF
Concomitant medication/ other therapies or medication for psoriasis:
• Topical therapy for psoriasis (eg, tar, corticosteroids, anthralin (dithranol), vitamin D analogues, retinoids) within 2 weeks prior to first administration of study medication with the exception of indifferent topical substances (eg, Vaseline), topical formulations containing salicylic acid (not more than 10%) or tar shampoos.
• Immunosuppressive agents, radiation therapy, chemotherapy or any specific systemic therapy for psoriasis (eg, methotrexate, cyclosporine, tacrolimus, steroids, retinoids, fumaric acid, biologicals) within 4 weeks (8 weeks for biologicals with a half-life longer than 2 days) prior to first administration of study drug OR the anticipated use of these therapies at any time during the study.
• Who are currently receiving or have received photochemotherapy/phototherapy (eg, PUVA, UVB, etc.) within 4 weeks prior to first administration of study drug.
2. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation.
3. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
4. Significant illness within the two weeks prior to dosing.
5. 5.A past medical history or family history of a prolonged QT-interval syndrome; clinically significant ECG findings including QTcB > 450 for males and > 470 for females, PR > 220, QRS > 110; hypokalemia or hypomagnesemia; history of heart failure or known left ventricular dysfunction (EF < 45%); history of clinically significant atrial arrhythmias eg atrial fibrillation, atrial flutter, supraventricular tachycardia) or ventricular arrhythmias; history of clinically significant atherosclerotic cardiovascular disease (eg, angina, coronary artery disease, history of MI or CVA).
6. History of autonomic dysfunction.
7. History of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
8. History of clinically significant drug allergy; history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug or drugs similar to the study drug.
9. History of malignancies including skin cancer or lymphoproliferative disorders
10. Who have hypertension (systolic BP >150 mmHg or diastolic BP >95 mmHg after 5 minutes in sitting or supine position) and who have other cardiovascular diseases requiring medical intervention. Subjects with drug-controlled hypertension are also excluded.
11. Other forms of psoriasis:
• Guttate, generalized erythrodermic, local or generalized pustular, or drug-associated (eg, beta-blockers, lithium) psoriasis.
• Psoriasis is limited to palmar/plantar areas.
12. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the subject in case of participation in the study. The investigator should be guided by evidence of any of the following:
• history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding;
• history of major gastrointestinal tract surgery such as gastrectomy, gastroentero-stomy, or bowel resection;
• history or clinical evi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method