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Phase 3 N=700 Randomized Triple-blind Treatment

Assessment of Efficacy and Safety in Patients With Non-cancer-related Pain and Opioid-induced Constipation

Opioid-Induced Constipation (OIC)

Enrolled (actual)
700
Serious AEs
4.9%
Results posted
Jun 2015
Primary outcome: Primary: Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12 — 81; 92; 68 Number of patients — p=0.202

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
NKTR-118 (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
AstraZeneca
Primary completion
Sep 2012

Outcome Measures

OutcomeResultp-value
PRIMARY
Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12
81; 92; 68 0.202
SECONDARY
Response (Responder/Non-responder) to Study Drug in the LIR Subgroup During Weeks 1 to 12
53; 58; 38 0.074
SECONDARY
Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours
19.3; 12.0; 37.2
SECONDARY
Change From Baseline in Mean Number of Days Per Week With at Least 1 SBM During Weeks 1 to 12
2.12; 2.41; 1.73 0.010 sig
SECONDARY
Change From Baseline in Degree of Straining
-0.67; -0.80; -0.48 0.005 sig
SECONDARY
Change From Baseline in Stool Consistency (Bristol Stool Scale)
0.54; 0.71; 0.26 0.001 sig
SECONDARY
Change From Baseline in Percent Numbers of Days With a CSBM (Complete Spontaneous Bowel Movement)
23.48; 27.20; 16.76 0.002 sig
SECONDARY
Change From Baseline in Mean Spontaneous Bowel Movements/Week
2.62; 3.14; 2.10 0.028 sig
SECONDARY
Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours in the Laxative Inadequate Response (LIR) Subgroup
12.8; 18.1; 38.2
SECONDARY
Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM)
-0.75; -0.81; -0.63; -0.67; -0.62; -0.72 0.080
SECONDARY
Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) Satisfaction Domain
-1.12; -1.30; -0.81 0.011 sig

Summary

The purpose of this study is to evaluate the effect and safety of NKTR-118 treatment of opioid-induced constipation in patients with non-cancer-related pain, including those patients that have inadequate response to laxative therapy (LIR).

Eligibility Criteria

Inclusion Criteria

  • Provision of written informed consent prior to any study-specific procedures.
  • Self-reported active symptoms of OIC at screening (<3 SBMs/week and experiencing ≥1 reported symptom of hard/lumpy stools, straining, or sensation of incomplete evacuation/anorectal obstruction in at least 25% of BMs over the previous 4 weeks); and Documented confirmed OIC (<3 SBMs/week on average over the 2-week OIC confirmation period.
  • Receiving a stable maintenance opioid regimen consisting of a total daily dose of 30 mg to 1000 mg of oral morphine, or equianalgesic amount(s) of 1 or more other opioid therapies for a minimum of 4 weeks prior to screening for non-cancer-related pain with no anticipated change in opioid dose requirement over the proposed study period as a result of disease progression.
  • Willingness to stop all laxatives and other bowel regimens including prune juice and herbal products throughout the 2-week OIC confirmation period and the 12-week treatment period, and to use only bisacodyl as rescue medication if a BM has not occurred within at least 72 hours of the last recorded BM.

Exclusion Criteria

  • Patients receiving Opioid regimen for treatment of pain related to cancer.
  • History of cancer within 5 years from first study visit with the exception of basal cell cancer and squamous cell skin cancer.
  • Medical conditions and treatments associated with diarrhea, intermittent loose stools, or constipation.
  • Other issues to the gastrointestinal tract that could impose a risk to the patient.
  • Pregnancy or lactation.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01323790). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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