Official Title: “A Multi-Center, Multinational, Randomized, Double-Blind, Parallel Group Study of the Effects of Ciclesonide Hfa-Mdi 640 μg/Day and Beclomethasone Hfa-Mdi 640 μg/Day on Lens Opacification in Adult Subjects With Moderate to Severe Persistent Asthma”

The primary objective is to demonstrate the non-inferiority of ciclesonide compared to beclomethasone-HFA in the occurrence of Class 1 lens event for nuclear (NO), cortical (C), or posterior subcapsular (P) lens opacification within 12 months. Secondary objectives are to compare ciclesonide and beclomethasone with respect to class II and class III best corrected visual acuity and intraocular pressure from baseline to 12 months.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety Study

Study Primary Completion Date: June 2005

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.

Intervention(s) in this Clinical Trial

• Drug: ciclesonide (XRP1526)

Primary Measures

• The primary endpoint is the occurrence of a Class I lens event for nuclear (NO), cortical (C), or posterior subcapsular (P) lens opacification within 12 months.
• A Class I lens event is defined as any of the following events in either eye:
• - 1.Increase from baseline in LOCS III grade of ≥ 0.5 (NO), ≥ 0.8 (C), or ≥ 0.5 (P)
• - 2.Cataract surgery

Secondary Measures

• - 1.Change from baseline to Month 12 in LOCS III grade for (a) nuclear opalescence, (b) cortical opacity, and (c) posterior subcapsular opacity.
• - 2.Occurrence within 12 months in either eye of a Class II lens event: Increase from baseline in LOCS III grade of ≥ 0.9 (NO), ≥ 1.5 (C), or ≥ 0.9 (P), or cataract surgery.
• - 3.Occurrence within 12 months in either eye of a Class III lens event: LOCS III grade ≥ 2.0 for any type of opacity (NO, C, or P) and a change in LOCS III grade of ≥ 0.9 for NO, ≥ 1.5 for C, and ≥ 0.9 for P, or cataract surgery.
• - 4.Change from baseline to Month 12 in best-corrected visual acuity.
• - 5.Change from baseline to Month 12 in intraocular pressure (mm Hg).
• Tertiary endpoint:
• - Change in post-bronchodilator FEV1 from baseline to Month 12.

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).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sanofi-Aventis

Overall Clinical Trial Officials and Contacts

ICD CSD Study Director Sanofi-Aventis  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00254956

Study ID Number: SFY6160

ClinicalTrials.gov Identifier: NCT00254956

Health Authority: United States: Food and Drug Administration