A Single Centre Study in Healthy Volunteers to Optimise the Rotacap Formulation and ROTAHALER Device for Delivery of Fluticasone Propionate/Salmeterol

Summary

The purpose of this study is to optimise the device and/or formulation of the Fluticasone propionate (FP)/salmeterol (SALM) unit dose powder inhaler (Rotahaler) to achieve drug delivery characteristics comparable to the Fluticasone propionate /salmeterol DISKUS inhaler. The indication is asthma and chronic obstructive pulmonary disease. The study is an open-label, randomised, cross-over, single centre study in healthy volunteers and will be conducted in a maximum of 3 parts, A, B and C. The design is adaptive and pharmacokinetic (PK) data analysis follows each part to enable a decision on whether progression to the subsequent parts is required. Part A of the study will test an alternative version of the Rotahaler with a low airflow resistance. The study will then test one or more of the following options depending on the outcome of part A. If progressed, part B will test modified Rotacap formulations including: (1) modified blend formulation, (2) reduced capsule fill weights, (3) different capsule types. Part B will also test other versions of the Rotahaler with intermediate airflow resistance. Part C will test the lower strength FP/salmeterol (100/50 mcg or lower) and/or a new unit dose DPI device (BUDI). A total of 36 subjects will be enrolled in each part to ensure 32 complete. In each cross-over arm, subjects will be administered 7 doses (3.5 days bid) with PK sampling following administration of the 7th dose. A three-day minimum wash-out period will separate each cross-over arm.

Timeline

Start

2012-01-16

Primary completion

2012-09-04

Completion

2012-09-04

Publications

• Background Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J; TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007 Feb 22;356(8):775-89. doi: 10.1056/NEJMoa063070.
• Background Celli BR, MacNee W; ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004 Jun;23(6):932-46. doi: 10.1183/09031936.04.00014304. No abstract available.
• Background Ferguson GT, Anzueto A, Fei R, Emmett A, Knobil K, Kalberg C. Effect of fluticasone propionate/salmeterol (250/50 microg) or salmeterol (50 microg) on COPD exacerbations. Respir Med. 2008 Aug;102(8):1099-108. doi: 10.1016/j.rmed.2008.04.019. Epub 2008 Jul 9.
• Background GINA: Global strategy for asthma management and prevention. NHLBI/WHO/GARD, Washingon DC 2006-updated 2009.
• Background GlaxoSmithKline Document Number RM2007/00413/03. CCI18781+GR33343 Investigator's Brochure, version number 12, dated 4 May 2011.
• Background GlaxoSmithKline document number YM2010/00082/02 Study ASR114334: A comparative bioavailability study to compare the pharmacokinetics and pharmacodynamic effects of Fluticasone propionate and Salmeterol delivered by Fluticasone propionate/ Salmeterol combination in a capsule-based inhaler and a multi-dose dry powder inhaler, in patients with moderate asthma and patients with moderate to severe COPD.
• Background GOLD 2006 Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2006)-updated 2009.
• Background James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee WM. Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure. Drug Metab Dispos. 2009 Aug;37(8):1779-84. doi: 10.1124/dmd.108.026195. Epub 2009 May 13.
• Background Kardos P, Wencker M, Glaab T, Vogelmeier C. Impact of salmeterol/fluticasone propionate versus salmeterol on exacerbations in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007 Jan 15;175(2):144-9. doi: 10.1164/rccm.200602-244OC. Epub 2006 Oct 19.
• Background Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm. 1987 Dec;15(6):657-80. doi: 10.1007/BF01068419.
• Results GlaxoSmithKline document number 2011N112456_00 Study report for A comparative bioavailability study to compare the pharmacokinetics and pharmacodynamic effects of fluticasone propionate and salmeterol delivered by fluticasone propionate/salmeterol combination in a capsule-based inhaler and a multi-dose dry powder inhaler, in patients with moderate asthma and patients with moderate to severe COPD.

Drugs

Indications