Does a Nasal Instillation of Miglustat Normalize the Nasal Potential Difference in Cystic Fibrosis Patients ?

Miglustat is an inhibitor of α-glucosidases and other enzymes. Oral miglustat is currently marketed in Europa and US for the treatment of Gaucher type 1 patients for whom enzyme replacement treatment is not an option.

Gastro-intestinal side effects are common with this formulation. This medication has been shown to have a beneficial effect both on Cl- an Na+ transports in cystic fibrosis epithelial cells. In addition, a single airway delivery of low-dose Miglustat normalizes nasal potential difference (NPD) in F508del cystic fibrosis mice. NPD abnormalities specific of CF patients are considered to reflect the primary defect of CFTR protein so that any curative treatment is expected to correct them at least partially.

In the field of respiratory pharmacology, it is a general rule that the inhaled route is to be favoured whenever possible : it is usually more effective despite much lower doses and systemic absorption (which also implies lower costs and improved tolerance).

The aim of this study is to investigate the effect of a single local administration of Miglustat on NPD measurements in CF patients homozygous for the F508del mutation.

Inclusion criteria

• Cystic fibrosis patients homozygous for the F508del mutation as confirmed by genetic test
• Aged 14 years and older
• Male or female (non-pregnant women who are to remain non-pregnant for 3 months after the end of the study)
• FEV1 > 50% of predicted normal

Exclusion criteria

• Acute respiratory tract infection or pulmonary exacerbation requiring antibiotic intervention within 2 weeks of visit 1
• Any condition prohibiting the correct measurement of the NPD such as respiratory tract infection
• Active or passive smoking
• Allergic chronic rhinitis
• History of significant lactose intolerance
• History of neuropathy
• History of cataracts or known increased risk of cataract formation
• Hypersensitivity to miglustat or any excipients
• Planned treatment or treatment with another investigational drug or therapy within 1 month prior to randomisation