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S. CUDMORE ET AL.
Table 3. Summary of subject baseline constipation characteristics and use of laxatives in the two weeks prior to the intervention.
Lepicol ( n ¼ 35) No. of subjects (%)
Placebo ( n ¼ 34) No. of subjects (%)
Total ( n ¼ 69) No. of subjects (%)
Baseline characteristics
p Value
Rome III criteria Straining during at least 25% of defecations? Have lumpy or hard stools in at least 25% of defecations? Have the sensation of incomplete evacuation for at least 25% of defecations? Have the sensation of anorectal obstruction/blockage for at least 25% of defecations? Use manual manoeuvers to facilitate at least 25% of defecations (e.g. digital evacuation, support of the pelvic floor)? Are loose stools rarely present without the use of laxatives? Does the subject have insufficient criteria for irritable bowel syndrome? Fewer than 3 defecations per week?
1.000 a 1.000 a
33 (94.3%) 33 (94.3%)
34 (100.0%) 34 (100.0%)
67 (97.1%) 67 (97.1%)
1.000 a
35 (100.0%)
34 (100.0%)
69 (100.0%)
1.000 a
8 (22.9%)
8 (23.5%)
16 (23.2%)
1.000 a
4 (11.4%)
3 (8.8%)
7 (10.1%)
1.000 a 1.000 a
35 (100.0%) 35 (100.0%)
34 (100.0%) 34 (100.0%)
69 (100.0%) 69 (100.0%)
1.000 a
35 (100.0%)
34 (100.0%)
69 (100.0%)
Laxative use Reported use of laxatives
< .001 a < .001 b
70 (78.7%) 2.00±1.41 1.91±0.51
19 (21.3%) 0.56±0.75 1.85±0.47
89 (100.0%) 1.29±1.14 1.89±0.49
Average reported use of laxatives per subject Average no. of bowel movements per week
.525 c For Rome III criteria, data are expressed as no. of individuals (% of the total no. of individuals in that group) who reported each symptom. Reported use of laxatives is the total number of reported uses for all the subjects during the pre-treatment, and the (% of the total use). Average reported use of laxa- tives per subject and Average no. of bowel movements are the mean ± SD.
a Binomial test. b Poisson-test. c Mann – Whitney test.
Secondary endpoints The secondary endpoints included to establish if Lepicol V R could: (i) improve stool consistency, as measured by the Bristol Stool Form Scale, where subjects recorded consistency in the daily diary; (ii) improve subjects ’ quality of life as measured by the PAC-QOL questionnaire; (iii) improve subjects ’ con- stipation symptoms as measured by the PAC-SYM questionnaire; (iv) reduce laxative use by the subjects. Safety assessments The clinical team assessed each subject-reported adverse event (AE) and categorised it according to severity into one of three categories; mild, moderate or severe. Its relationship to the study treatment was also determined as unrelated, possible or definite. Statistical methods and data analysis Sample size was calculated using SAS Statistical soft- ware (SAS Institute Inc., Cary, NC) based on increas- ing bowel movements per week, which was defined as the primary outcome in the current study. For a
visits (visits 2 and 3) subjects also completed the fol- lowing validated questionnaires – Patient Assessment of Constipation Symptoms (PAC-SYM) (Frank et al. 1999) and Patient Assessment of Constipation – Quality of Life (PAC-QOL) (Marquis et al. 2005). The PAC-SYM questionnaire is a 12-item self-report instrument divided into abdominal, rectal and stool symptoms. Items were rated on a 5-point Likert scale (0 – 4) with responses scored from 0 (absence of symp- tom) to 4 (very severe symptoms). The abdominal, rectal and stool domain scores are the mean scores of each domain. The overall score is the mean of all 12 items. The PAC-QOL is a 28 item questionnaire with four subscales (worries and concerns, physical discom- fort, psychosocial discomfort, and satisfaction) and an overall scale, providing a comprehensive assessment of the burden of constipation on patients' everyday func- tioning and well-being. Both questionnaires have been validated and shown to be internally consistent, repro- ducible, valid and responsive to improvements over time (Frank et al. 1999; Marquis et al. 2005).
Primary endpoint The primary endpoint was to evaluate if Lepicol could increase the number of bowel movements by 1.5 per week versus placebo by week 4 of the treatment.
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