Pruritus
Conditions
Interventions
Product Code: DNK333
Pharmaceutical Form: Oral emulsion
CAS Number: 1035662-71-5
Current Sponsor code: DNK333 semihydrate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Co
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female atopic dermatitis patients, 18 to 60 years of age inclusive, who fulfill the following criteria at baseline: • Requirement of systemic therapy • Itch VAS score higher than 50 mm • EASI score higher than 8 2. Normal vital signs (systolic and diastolic blood pressure and pulse rate) assessed at screening and baseline in the sitting position after the subject has rested for at least three (3) minutes, and again when required after 3 minutes in the standing position. 3. All female subjects must have negative pregnancy test results at screening and at baseline. Female subjects of childbearing potential must be using two highly effective methods of contraception from the time of screening and for the duration of the study, through study completion. 4. Male subjects must be using two acceptable methods of contraception (e.g., spermicidal gel plus condom), for the entire duration of the study up to the study completion visit, and refrain from fathering a child in the 3 months following the last study drug administration. 5. Subjects must weigh at least 50 kg, and must have a body mass index within the range of 17 to 35 kg/m2. 6. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent. 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
Exclusion criteria
Exclusion criteria: 1. Pregnant or breastfeeding women. 2. Any systemic immunosuppressive treatment and/or phototherapy within 4 weeks prior to the first dosing. 3. Use of any systemic antihistamines or topical corticosteroids within one week prior to first dosing and for the duration of the treatment period. Any other topical or oral treatment for atopic dermatitis (except emollients prescribed by the investigator) within 2 weeks prior to the first dosing will also be excluded. 4. Use of any prescription drugs within 2 weeks prior to initial dosing, and/or over-the-counter (OTC) medication, herbal supplements, and/or dietary supplements (vitamins included) within 2 weeks prior to initial dosing. Exceptions being: • NSAID’s (non steroidal anti-inflammatory drugs) as an incidental and limited need • Short-acting ß2-adrenergic receptor antagonists (e.g. salbutamol) as needed (e.g. allergic asthma) • Topical antihistamines (eye drops and/or nose sprays) at stable dose (started at least 1 week prior to Baseline visit and maintained for the duration of the treatment period). • Antihypertensive drugs: calcium channel blockers and angiotensine II receptor antagonists at stable dose (started at least 4 weeks prior to Baseline visit and maintained for the duration of the whole treatment period) • Thyroid hormones at stable dose (started at least 4 weeks before Baseline visit and maintained for the duration of the entire treatment period) 5. Participation in any clinical investigation within 4 weeks prior to initial dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations. 6. Donation or loss of 400 mL or more of blood within 8 weeks prior to initial dosing, or longer if required by local regulation. 7. Significant illness within 2 weeks prior to initial dosing. 8. A past medical history of clinically significant ECG abnormalities. 9. Recent (within the last 3 years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc). 10. History of allergy to the investigational compound/compound class being used in this study. 11. Any history of restless leg syndrome, tremors or insomnia or any medical condition that causes increased nocturnal movement. 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. 13. WBC count must be within normal reference range of the laboratory. 14. History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result. 15. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. 16. History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening and at baseline. 17. Subjects who have been committed to an institution by way of official or judicial order will be excluded from participation to the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To investigate the efficacy of 4 different DNK333 doses (1, 5, 25 and 100 mg bid) over 2 weeks with respect to reduction in pruritus, as assessed by actigraphy and Visual Analog Scale (VAS) ;Secondary Objective: • Evaluate the therapeutic benefit form the patient’s perspective of multiple doses (1, 5, 25 and 100 mg bid) of DNK333 to reduce pruritus as assessed by the Patient Benefit Index for Pruritus (PBIfP) • Determine the efficacy of multiple doses (1, 5, 25 and 100 mg bid) of DNK333 to reduce dermatitis as measured with the atopic dermatitis score, the Eczema Area Severity Index (EASI) • Determine safety and tolerability of multiple doses (1, 5, 25 and 100 mg bid) of DNK333 in atopic dermatitis patients. • Determine the plasma pharmacokinetics and skin exposure following treatment of atopic dermatitis patients with multiple doses (1, 5, 25 and 100 mg bid) of DNK333 • Assess the health-related quality of life by using the Quality of Life for Atopic Dermatitis (QoLIAD) score. • Compare the pharmacokinetics of DNK333 administered as an oral microemulsion drinking solution to a solid dispersion tablet in steady state. ;Primary end point(s): • Average nocturnal activity intensity (actigraphy) per hour, • Nocturnal activity counts above zero (actigraphy) per hour, and • VAS measurement of itch. | — |
Countries
Germany
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma AG
Outcome results
None listed