A randomized, open-label, parallel-group study to investigate blood concentrations, safety and tolerability of 2 ointment formulations of ASM981 in adult patients with atopic dermatitis treated topically for 2 weeks - A2308

• Conditions: Atopic dermatitis (atopic eczema)

• Registration Number: EUCTR2004-003798-94-AT
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2004-11-05
• Last Update Posted: 22 April 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1.Male and/or female patients with AD from 18-45 years of age.

2.Female subjects must have been surgically sterilized at least 6 months prior to screening. Female subjects of child bearing potential must be using a double-barrier local contraception, i.e. intra-uterine device plus condom, or spermicidal gel plus condom. Postmenopausal women must have no regular menstrual bleeding for at least 2 years prior to inclusion.

3.Subjects must fulfill the diagnostic criteria of Hanifin and Rajka for AD.

4.The severity of AD must be defined as moderate or severe by using the Investigator’s Global Assessment. The IGA score will be =3 and =4.
The extent of the disease will be determined by the rule of nine. AD must involve at least 30% of the subject’s body surface area.

5.Vital signs (after 3 minutes resting measured in the supine position) which are within the following ranges:
oral body temperature between 35.0-37.5 °C
systolic blood pressure, 90-140 mm Hg
diastolic blood pressure, 50-90 mm Hg
pulse rate, 40 - 90 bpm

6.Subject able to provide written informed consent prior to study participation.

7.Subjects able to communicate well with the investigator and comply with the requirements of the study.

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

1.Patients with very severe AD (IGA=5), Netherton’s syndrome or psoriasis.
2.Clinically significant findings except AD during the physical examination or laboratory abnormalities.
3.Symptoms of a significant clinical illness other than AD in the three-week period preceding the entry in the study.
4.Presence of any viral or fungal or untreated bacterial skin infection.
5.History of clinically significant drug allergy especially subjects with known serious adverse reactions or hypersensitivity to macrolides or with known hypersensitivity to any of the ingredients of the study medication.
6.Women who are pregnant or breast feeding and women who do not use double barrier contraception during and at least until 4 weeks after the end of treatment.
7.Use of any prescription drug or over-the-counter (OTC) medication within 2 weeks prior to dosing. Paracetamol is acceptable, but must be documented.
8.History of presence of malignancy, including skin cancer, or lymphoproliferative disorder.
9.Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation.
10.Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
11.History of autonomic dysfunction.
12.Use of systemic corticosteroids (i.e. oral, intravenous, intra-articular, rectal) within four (4) weeks prior to baseline. Phototherapy within four (4) weeks prior to baseline. Topical therapy (e.g. tar, topical corticosteroids, topical anti-fungals,) within 3 days prior to baseline, with the exception of emollients. Topical tacrolimus within 2 weeks prior to baseline.
13.Treatment with nephrotoxic drugs within two (2) weeks to baseline (aminoglycosides, amphotericin B, colchicine).
14.Treatment with any CYP3A4 inhibitors or inducers within two (2) weeks prior to baseline and during the study course (i.e. azole antifungals, macrolide antibiotics, dexamethasone, phenytoin, ritonavir, rifabutin, antiepileptic agents/barbiturates, cimetidine, St. John’s wort, etc.)
15.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:
•clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests such as SGOT, SGPT, GGT, alkaline phosphatase, or serum bilirubin. SGPT will have to be strictly within the normal range before inclusion, GGT and alkaline phosphatase must not exceed twice the upper limit of the normal range, and serum bilirubin should not exceed the value of 27 µmol/L (1.6 mg/dL).
•history or presence of impaired renal function as indicated by abnormal creatinine or BUN values or abnormal urinary constituents (e.g., albuminuria);
•polymorphonuclears <1500/µL or platelets <100’000/µL at inclusion.
16.History of immunocompromise, including a positive HIV (ELISA and Western blot) test result.
17.A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.
18.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 or baseline evaluations.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: •To evaluate the short-term safety and tolerability of 2 formulations of 1% pimecrolimus ointment when applied twice a day for 2 weeks on the lesional skin of patients with moderate to severe atopic dermatitis (AD).<br>•To measure the blood concentrations and pharmacokinetics of 2 formulations of 1% pimecrolimus ointment when applied twice a day for 2 weeks on a relevant extent of lesional skin (at least 30% of the total body surface area) in patients with moderate to severe AD.<br>;Secondary Objective: •To explore the efficacy of 2 formulations of 1% pimecrolimus ointment applied topically on the lesional skin of patients with moderate to severe AD.;Primary end point(s): The endpoints include pharmacokinetic endpoints to measure drug levels in patients, as well as safety/tolerability assessments.