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Phase 3 N=652 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)
652
Serious AEs
4.6%
Results posted
Jun 2015
Primary outcome: Primary: Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12 — 87; 95; 63 Number of patients — p=0.015

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
Aug 2012

Outcome Measures

OutcomeResultp-value
PRIMARY
Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12
87; 95; 63 0.015 sig
SECONDARY
Response (Responder/Non-responder) to Study Drug in the LIR Subgroup During Weeks 1 to 12
49; 57; 34 0.028 sig
SECONDARY
Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours
20.4; 5.9; 35.8
SECONDARY
Change From Baseline in Mean Number of Days Per Week With at Least 1 SBM During Weeks 1 to 12
2.21; 2.48; 1.66 <0.001 sig
SECONDARY
Change From Baseline in Degree of Straining
-0.64; -0.73; -0.54 0.176
SECONDARY
Change From Baseline in Stool Consistency (Bristol Stool Scale)
0.53; 0.66; 0.47 0.564
SECONDARY
Change From Baseline in Percent Numbers of Days With a CSBM (Complete Spontaneous Bowel Movement)
22.31; 27.04; 18.45 0.094
SECONDARY
Change From Baseline in Mean Spontaneous Bowel Movements/Week
2.56; 3.02; 2.02 0.011 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
20.6; 5.4; 43.4
SECONDARY
Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM)
-0.76; -0.81; -0.69; -0.61; -0.65; -0.63 0.273
SECONDARY
Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) Satisfaction Domain
-0.91; -1.06; -0.89 0.831

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.
  • Men and women who are between the ages of ≥18 and <85 years.
  • 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 (NCT01309841). 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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