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GSK Constipation Observational Trial

An Observational Study to Characterize the Burden of Illness Associated with Laxative Use in Subjects Using Opioids for the Management of Persistent Pain

Sponsor: GSK
Study Drug: None Protocol: ABD106919 Phase: Observational
CRO: CTMS
CRAs: Janet Looney (jlooney@ctmsinc.com) (423-968-9533)
Deborah Nunn (dnunn@ctmsinc.com) (423-968-9533)
IRB: LDR IRB
Subjects 500 /50 Sites -> 10 Subjects per Site
eCRF: InForm
CSBM -> Complete Spontaneous Bowel Movement: A BM that is not stimulated by a rescue medicine and is accompanied by the sensation of complete evacuation

Stimulant Laxatives
Stimulants cause rhythmic muscle contractions in the intestines. Brand names include: Correctol, Dulcolax (Bisacodyl or Sodium Picosulphate), Purge, Cascara, Castor Oil, Ex Lax and Senokot (senna).

Hyperosmolar Laxatives
Hyperosmolar laxatives are undigestible, unabsorbable compounds that remain within the colon and retain the water that already is in the colon by osmotically increasing intraluminal fluid. The result is softening of the stool. The most common hyperosmolar laxatives are: lactulose (e.g., Enulose, Sorbitol, Chronulac & Kristalose), sorbitol, glycerin (in suppository form) and polyethylene glycol (e.g., MiraLax & Golytely). They are available by prescription only. These laxatives are safe for long-term use and are associated with few side effects. Hyperosmolar laxatives may be digested by colonic bacteria and turned into gas, which may result in unwanted abdominal bloating and flatulence. This effect is dose-related. Therefore, gas can be reduced by reducing the dose of the laxative. In some cases, the gas will decrease over time.

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GSK Constipation Observational Trial

IC
Age ? 18
Using an Opioid for persistent pain
IC for Enrollment into the 1-week Screening Phase:
1. Using an Opioid 6-7 days in each of the last 4 weeks.
2. Use a Stimulant or Hyperosmotic Laxative at least 2 days each week for the last 4 weeks.
3. Opioid Induced Constipation
IC for Enrollment into the 8-week Longitudinal Phase:
1. Used a Stimulant or Hyperosmotic Laxative ? 25 % of days (2 days in 7) during the 1-week screening phase.
2. Demonstrated compliance ? 70% of days during the 1-week screening phase.
EC
IBD, functional bowel disorder, IBS
No Switching Laxatives to qualify for the study

Five Populations from the Screening Questionnaire (Q)
1. Subjects using Opioids for less than 1 month -> Finished 2. Subjects using Opioids equal/greater than 1 month without a history of constipation -> Q & Finished 3. Subjects using Opioids equal/greater than 1 month with a history of constipation -> Q & Proceed 4. Subjects using Opioids equal/greater than 1 month with a history of constipation who do not treat their constipation with a stimulant or hyperosmotic laxative. (In each of the last 4 wks failed to take Opioids 6-7 days AND/OR failed to use Stimulant or Hyperosmotic Laxatives equal/greater than 2 Days -> Finished)
5. Subjects using Opioids equal/greater than 1 month with a history of constipation who do treat their constipation with a stimulant or hyperosmotic laxative. (In each of the last 4 wks took Opioids 6-7 days AND used Stimulant or Hyperosmotic Laxatives equal/greater than 2 Days each wk -> Enter into One Week Screening Phase)

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GSK Constipation Observational Trial

V1 D -7 ICF (1 wk Screen/Cross-Sectional + 8 wk Longitudinal)
Opioid User Completes Screening Questionnaire;
. Enters One Week Screening Phase;
Using Laxative equal/greater than 25% (2 days in 7);
Compliant equal/greater than 70% Phone System

V-Phone D 0 Wk 0; Telephone call only;
Begin 8 Week Longitudinal Phase; +/-2 Days

V2 D 28 Wk 4; Review Pain Med & Laxative Log; +/-4 Days

V3 D 56 Wk 8; Final Visit +/- 4 Days