Figure 1. The proportion of CSBM responders over the 2-week treatment period (A), the proportion of SBM responders by ... Figure 1. The proportion of CSBM.

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Figure 1. The proportion of CSBM responders over the 2-week treatment period (A), the proportion of SBM responders by ... Figure 1. The proportion of CSBM responders over the 2-week treatment period (A), the proportion of SBM responders by week (B), and the proportion of CSBM responders by week (C) in COMPOSE-4 (proportion ± 95% CI; FAS). *P < 0.0001 versus placebo. CI, confidence interval; CSBM, complete spontaneous bowel movement; FAS, full analysis set; SBM, spontaneous bowel movement. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Ann Oncol, Volume 29, Issue 6, 18 April 2018, Pages 1461–1467, https://doi.org/10.1093/annonc/mdy118 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 2. Proportion of subjects with ≥ 1 SBM (A) or ≥ 1 CSBM (B) at specific time points within 24 h after the initial ... Figure 2. Proportion of subjects with ≥ 1 SBM (A) or ≥ 1 CSBM (B) at specific time points within 24 h after the initial dose of the study drug in COMPOSE-4 (proportion ± 95% CI; FAS). *P < 0.0001 versus placebo. CI, confidence interval; CSBM, complete spontaneous bowel movement; FAS, full analysis set; SBM, spontaneous bowel movement. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Ann Oncol, Volume 29, Issue 6, 18 April 2018, Pages 1461–1467, https://doi.org/10.1093/annonc/mdy118 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 3. Kaplan–Meier curve of time to first SBM (A) or CSBM (B) in COMPOSE-4 (FAS). Circles represent censored time. ... Figure 3. Kaplan–Meier curve of time to first SBM (A) or CSBM (B) in COMPOSE-4 (FAS). Circles represent censored time. The time to the first SBM or CSBM was censored for subjects who withdrew from the study before an SBM or CSBM was observed, or if no SBM or CSBM occurred during the 2-week treatment period. CSBM, complete spontaneous bowel movement; FAS, full analysis set; SBM, spontaneous bowel movement. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Ann Oncol, Volume 29, Issue 6, 18 April 2018, Pages 1461–1467, https://doi.org/10.1093/annonc/mdy118 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 4. Change from baseline to day 15 of COMPOSE-4 in PAC-SYM (A) and PAC-QOL (B) overall scores and scores for each ... Figure 4. Change from baseline to day 15 of COMPOSE-4 in PAC-SYM (A) and PAC-QOL (B) overall scores and scores for each domain [mean (SD); FAS]. *P = 0.045 versus placebo. <sup>†</sup>P = 0.015 versus placebo. FAS, full analysis set; ns, not significant; PAC-QOL, Patient Assessment of Constipation Quality of Life; PAC-SYM, Patient Assessment of Constipation Symptoms; SD, standard deviation. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Ann Oncol, Volume 29, Issue 6, 18 April 2018, Pages 1461–1467, https://doi.org/10.1093/annonc/mdy118 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 5. Change from baseline (predose on day 1 of COMPOSE-4) over time in PAC-SYM (A) and PAC-QOL (B) overall scores ... Figure 5. Change from baseline (predose on day 1 of COMPOSE-4) over time in PAC-SYM (A) and PAC-QOL (B) overall scores and scores for each domain in COMPOSE-5 (mean; FAS). *P ≤ 0.03 versus BL for mean overall scores and scores for each domain of PAC-SYM. <sup>†</sup>P ≤ 0.0001 versus BL for mean overall scores and scores for each domain of PAC-QOL. BL, baseline; FAS, full analysis set; PAC-QOL, Patient Assessment of Constipation Quality of Life; PAC-SYM, Patient Assessment of Constipation Symptoms. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Ann Oncol, Volume 29, Issue 6, 18 April 2018, Pages 1461–1467, https://doi.org/10.1093/annonc/mdy118 The content of this slide may be subject to copyright: please see the slide notes for details.