TABLE 7.
Summary of statistical analysis of plasma pharmacodynamics biomarkers
| Biomarker | Least square means % baseline±sem | Difference in least square means % baseline (95% CI)# | Two-sided p-value# | Bayesian probability of effect# | |||
| Placebo | 0.3 mg | 3 mg | 10 mg | ||||
| PDGF-BB | 275.2±42.2 | 90.5±55.2 | 103.7±54.1 | 35.7±54.2 | −239.5 (−384.8– −94.2) | 0.003 | 99.86 |
| PAI-1 | 197.6±32.7 | 84.6±48.8 | 92.4±44.5 | 45.8±43.7 | −151.8 (−265.3– −38.2) | 0.012 | 99.43 |
| Gal-3 (BAL) | 81.7±9.0 | 67.9±12.1 | 43.0±11.7 | 37.1±13.5 | −44.6 (−80.4– −8.8) | 0.017 | 99.14 |
| Gal-3 | 121.0±15.6 | 113.9±21.2 | 119.5±21.3 | 53.4±23.5 | −67.6 (−126.9– −8.4) | 0.028 | 98.63 |
| CCL18 (PARC) | 109.5±8.8 | 89.6±11.8 | 98.9±12.0 | 74.6±11.8 | −35.0 (−65.8– −4.2) | 0.028 | 98.59 |
| YKL-40 (CHI3L1) | 80.4±7.9 | 84.1±12.5 | 50.2±18.6 | 51.6±10.4 | −28.9 (−55.9– −1.9) | 0.037 | 98.13 |
| MMP-8 | 176.9±39.3 | 138.0±52.8 | 115.2±52.7 | 51.5±56.1 | −125.4 (−271.3–20.5) | 0.088 | 95.60 |
| PDGF-AA | 213.3±45.6 | 61.7±60.6 | 117.1±62.1 | 83.6±61.2 | −129.7 (−295.3–35.8) | 0.117 | 94.13 |
| HGF | 110.3±12.6 | 100.3±17.5 | 103.2±16.9 | 73.2±18.8 | −37.2 (−85.5–11.2) | 0.124 | 93.79 |
| MMP-1 | 164.2±42.0 | 67.3±56.3 | 107.1±59.1 | 62.1±58.1 | −102.1 (−251.4–47.3) | 0.169 | 91.55 |
| CCL2 (MCP-1) | 161.1±29.6 | 126.7±39.3 | 93.7±38.7 | 89.4±43.5 | −71.7 (−187.1–43.7) | 0.209 | 89.55 |
| CCL5 (RANTES) | 129.9±25.7 | 62.3±37.1 | 115.1±35.1 | 75.8±35.8 | −54.1 (−147–38.8) | 0.238 | 88.10 |
| MIF | 194.1±62.2 | 123.6±83.6 | 95.9±83.9 | 73.9±83.7 | −120.2 (−339.2–98.9) | 0.265 | 86.74 |
| MMP-7 | 166.4±44.6 | 79.3±59.2 | 82.3±58.4 | 84.4±58.7 | −82.0 (−237.9–73.9) | 0.285 | 85.76 |
| PTX3 | 136.5±41.8 | 51.8±68.6 | 74.2±53.1 | 67.0±56.1 | −69.6 (−220.3–81.2) | 0.343 | 82.88 |
| Osteopontin | 118.1±17.9 | 106.2±23.9 | 84±23.7 | 91.3±23.4 | −26.8 (−88.0–34.3) | 0.370 | 81.50 |
| Periostin | 98.4±3.7 | 114.0±5.3 | 99.3±5.2 | 93.1±5.0 | −5.4 (−18.8–8.0) | 0.412 | 79.42 |
| Gal-1 | 106.4±12.4 | 93.1±16.7 | 120.2±16.6 | 89.7±16.6 | −16.6 (−60.0–26.7) | 0.431 | 78.45 |
| IL-13 | 105.2±6.6 | 87.4±8.8 | 100.4±9.5 | 97.6±8.8 | −7.6 (−30.4–15.2) | 0.496 | 75.22 |
| SP-D | 114.7±12.0 | 109.6±16.6 | 111.7±18.2 | 118.7±17.3 | 4.0 (−41.0–49.1) | 0.854 | 42.67 |
| IL-1ra | 92.0±15.0 | 93.2±20.3 | 98.7±20.2 | 98.0±20.8 | 6.0 (−47.5–59.4) | 0.818 | 40.89 |
| TIMP-1 | 102.2±4.1 | 88.6±5.8 | 107.0±6.0 | 106.0±5.5 | 3.8 (−10.6–18.2) | 0.583 | 29.17 |
PDGF: platelet-derived growth factor; PAI: plasminogen activator inhibitor; Gal: galectin; BAL: bronchoalveolar lavage; CCL: chemokine (C-C motif) ligand; PARC: pulmonary and activation-regulated chemokine; CHI3L1: chitinase-3-like protein 1; MMP: matrix metalloproteinase; HGF: hepatocyte growth factor; MCP: monocyte chemoattractant protein; RANTES: regulated on activation, normal T-cell expressed and secreted; MIF: macrophage migration inhibitory factor; PTX: pentraxin; IL: interleukin; SP-D: surfactant protein D; ra: receptor antagonist; TIMP: tissue inhibitor of metalloproteinases; CXCL: chemokine (C-X-C motif) ligand. For the following biomarkers, the majority of values were below the lower level of quantification and therefore were not analysed: amphiregulin, CCL26 (eotaxin), CXCL1 (GROα), CXCL10 (IP-10), epidermal growth factor, IL-8, IL-10, IL-25, IL-33, interferon-γ and tumour necrosis factor-α. #: results from an ANCOVA model including effects for treatment group and baseline value with the Bayesian probability of effect of the 10 mg TD139 group versus placebo shown.