Effects Of Ciclesonide And Beclomethasone On Lens Opacification In Adult Subjects With Moderate To Severe Persistent Asthma

This is a multi-center, multinational, active-controlled, double-blind, randomized (1:1) parallel group study of the effects of inhaled ciclesonide HFA-MDI 640 mcg/day and beclomethasone HFA-MDI 640 mcg/day on lens opacification in adult subjects with moderate to severe persistent asthma. The study consists of a 1-14 day screening phase during which subject eligibility will be determined, followed by a 12-month double-blind treatment phase. Lens opacification will be evaluated by slit lamp examination performed after pupillary dilation to at least 6.0 mm before randomization and after 4 months, 8 months, and 12 months of treatment using the LOCS III system for grading lens opacities. Best-corrected visual acuity and intraocular pressure will be measured at each eye examination visit. An Independent Data Monitoring Committee (IDMC) will be constituted to monitor safety throughout the double-blind treatment phase.

Inclusion criteria

• Males or non-pregnant, non-lactating females 18 years of age and older with a history of moderate to severe persistent asthma for a duration of at least 2 months prior to screening.
• At screening, FEV1 must be ≥ 40% and ≤ 85% of predicted.
• Documented use of inhaled corticosteroid therapy at any dose for at least 1 month prior to screening.
• Able to demonstrate acceptable oral inhaler technique.
• Non-smoker for at least the past year and less than a 10 pack-year smoking history if previous smoker.
• Written informed consent agreement.

Exclusion criteria

• History of prior cataract surgery in either eye.
• Evidence of congenital cortical cataract.
• Inability to grade nuclear, cortical, or posterior subcapsular opacities in either eye with LOCS III at the baseline slit lamp examination.
• Inability to dilate pupils to at least 6.0 mm.
• Nuclear opalescence with a LOCS III grade ≥ 4 in either eye at the baseline slit lamp examination.
• Cortical lens opacities with a LOCS III grade ≥ 3 in either eye at the baseline slit lamp examination.
• Posterior subcapsular lens opacities with a LOCS III grade ≥ 2 in either eye at the baseline slit lamp examination.
• Elevated intraocular pressure requiring treatment
• Best corrected visual acuity less than 74 letters (equivalent to vision worse than 20/30) in either eye at baseline.
• Females who are pregnant or lactating or have a positive pregnancy test at Visit 1 (Screening).
• Have had more than 1 in-patient hospitalization in the past year for asthma exacerbations.
• Have had more than 2 bursts of oral steroids per year for each of the past 2 years prior to screening.
• Chronic use of oral, injectable, or topical steroids except for inhaled corticosteroids for any condition. Topical corticosteroids designated as having a mild potency by the Stoughton-Cornell Scale or the European Guideline for levels of corticosteroid activity are allowed (see AppendixG).
• Any chronic condition that is likely to require treatment with oral or systemic corticosteroids other than asthma (e.g. systemic lupus, inflammatory bowel disease, rheumatoid arthritis).
• Topical ocular steroid treatment within 3 months prior to screening.
• Chronic or recurrent inflammatory disease in either eye likely to result in visual abnormalities or require treatment with ocular steroids.
• History of drug or alcohol abuse.
• Any clinically significant medical condition that would interfere with the subject's ability to participate in and comply with study protocol.
• Subject unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study.
• Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.
• Hypersensitivity to the investigational products or to drugs with similar chemical structures.
• Have been treated with any investigational drug/product within 30 days prior to Visit 1 (Screening).