Cilomilast 181.

Study characteristics
Methods	Study design: parallel‐group study Randomisation: randomised, double‐blind, placebo‐controlled trial Trial duration: 13 weeks Analysis was done on the per‐protocol population
Participants	Setting: 27 centres in Australia, Canada, Finland, Ireland, Lithuania, Norway, Romania, Slovakia, Slovenia, South Africa, Sweden, and the UK Participants: 127 (15 mg cilomilast: 65, placebo: 62) Baseline characteristics: mean age 63.4 years placebo and 61.4 years cilomilast, 76% male placebo and 72% male cilomilast Inclusion criteria: aged 40 to 80 years, FEV₁/FVC ≤ 0.7 with smoking history > 10 pack‐years, post‐bronchodilator FEV₁ between 40% and 80% predicted normal, poor reversibility of ≤ 10% or 200 mL increase in FEV₁ Exclusion criteria: not stated Total numbers of participant withdrawals: 8 (12%) and 6 (10%) from treatment and control groups, respectively
Interventions	Run‐in: not stated Cilomilast 15 mg twice daily Placebo twice daily Concomitant medication Short‐acting anticholingeric: no information available SABA: no information available Corticosteroid: no information available LABA: no information available
Outcomes	Primary outcomes: change from baseline at endpoint in CD68+ (macrophages) and CD8+ (cytotoxic T lymphocytes) per unit area of tissue Secondary outcomes: change from baseline in numbers of subepithelial cells per unit area in biopsy for neutrophil elastase‐positive (ne+) cells, CD4+, IL‐8 mRNA‐positive cells, TNF‐alpha mRNA‐positive cells
Notes	Funded by GlaxoSmithKline
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A central randomisation schedule that was balanced at site level. An interactive voice response system was used to generate a random number to assign eligible participants
Allocation concealment (selection bias)	Low risk	Assumed that the allocation concealment method was adequate due to pharmaceutical company sponsorship
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The trial was double‐blind. Participants and personnel were blind to which treatment they were assigned to. Cilomilast and matched placebo tablets were identical in appearance, and only the double‐blind medication included the container number
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Assumed that this would be low risk; however, no available information
Incomplete outcome data (attrition bias) All outcomes	Low risk	Total numbers of participants withdrawn 6 (10%) placebo, 8 (12%) cilomilast
Selective reporting (reporting bias)	Low risk	Outcomes were reported as planned. Trial information was reported on the GSK website only
Other bias	Low risk	No information on baseline anticholinergic, beta₂‐agonist, or corticosteroid use