Proof of concept study: does fenofibrate have a role in sleep apnoea syndrome?

Abstract

Objective:

To investigate the effect of fenofibrate on sleep apnoea indices.

Methods:

Proof-of-concept study comprising a placebo run-in period (1 week, 5 weeks if fibrate washout was required) and a 4-week randomized, double-blind treatment period. Thirty-four subjects (mean age 55 years, body mass index 34 kg/m², fasting triglycerides 3.5 mmol/L) with diagnosed sleep apnoea syndrome not treated with continuous positive airways pressure were enrolled and randomized to once daily treatment with fenofibrate (145 mg NanoCrystal® tablet) or placebo. Overnight polysomnography, computerized attention/vigilance tests and blood sampling for measurement of lipids, insulin, fasting plasma glucose and fibrinogen were performed at the end of each study period.

Clinical trial registration:

NCT00816829.

Main outcome measures:

As this was an exploratory study, a range of sleep variables were evaluated. The apnoea/hypopnoea index (AHI) and percentage of time spent with arterial oxygen saturation (SpO₂) <90% were relevant as they have been evaluated in other clinical trials. Other variables included total apnoeas, hypopnoeas and oxygen desaturations, and non-cortical micro-awakenings related to respiratory events per hour.

Results:

Fenofibrate treatment significantly reduced the percentage of time with SpO₂ <90% (from 9.0% to 3.5% vs. 10.0% to 11.5% with placebo, p = 0.007), although there was no significant change in the AHI (reduction vs. control 14% (95%CI −47 to 40%, p = 0.533). Treatment reduced obstructive apnoeas (by 44%, from 18.5 at baseline to 15.0 at end of treatment vs. 29.0 to 30.5 on placebo, p = 0.048), and non-cortical micro-awakenings per hour (from 23.5 to 18.0 vs. 24.0 to 25.0 with placebo, p = 0.004). Other sleep variables were not significantly influenced by fenofibrate.

Key limitations:

Exploratory study in patients with mild to moderate sleep apnoea, limited treatment duration; concomitant hypnotic treatment (35%); lack of correction for multiplicity of testing.

Conclusions:

The consistent direction of change in sleep indices in this proof-of-concept study may support further investigation of fenofibrate in moderate to severe sleep apnoea syndrome.

Key words::

• Fenofibrate
• Fibrinogen
• Oxygen desaturation
• Sleep apnoea syndrome
• Triglycerides

Transparency

Declaration of funding

This study was supported by a grant from Laboratories Fournier SA, Daix, France.

Declaration of financial/other relationships

E.B. has received consultancy fees from MSD-SP, Pfizer, AstraZeneca, Novo Nordisk, Danone, Unilever, AMT, Ethypharm, Lilly, Takeda, Sanofi-Aventis for participation in advisory boards and presentations at medical meetings, and grants for research from Fournier, MSD-SP, GENFIT, Novartis, Unilever, GSK, Pfizer and AstraZeneca. B.H. has received consultancy fees from Pfizer, Céphalon, Novo Nordisk, Lilly, MSD-SP, Unilever, Lesieur and Abbott for participation in advisory boards and presentations at medical meetings, and grants for research from AstraZeneca, Sanofi and Pfizer. E.D., D.B.R. and B.G. report no conflict of interest. J.-C.A. and A.D. are employees of Laboratories Fournier SA.

Peer reviewers may receive honoraria from CMRO for their review work. Peer reviewer 1 has disclosed no relevant financial relationships. Peer reviewer 2 has disclosed that he/she has received research funding from Merck Schering Plough; and has acted as an advisor to/or sat on a speakers bureau for AstraZeneca, Gilead, GlaxoSmithKline, Merck Sharpe & Dohme, Genzyme, LifeCycle Pharma and SurfaceLogix.

Acknowledgements

We acknowledge data management and statistical analysis performed by Fournier SA (A. Dubois and C. Javierre), and editorial assistance (C. Marquer, J. Stock; the latter was funded by a non-educational grant from Fournier SA). We would like to thank all clinical research personnel and subjects who participated in this study.