Opioid-Induced Constipation
Conditions
Keywords
Cancer-Related Pain, Opioid-Induced Constipation, OIC
Brief summary
The purpose of this study is to compare the effect of NKTR-118 with placebo in the treatment of opioid-induced constipation (OIC) in patients with cancer-related pain, including those patients that have inadequate response to laxative therapy (LIR). The study consists of 2 parts; A initial 4-week treatment period (part A) and then a 12 week extension with active treatment (part B).
Interventions
DRUGNKTR-118
12.5 mg oral tablet once daily
DRUGPlacebo
Oral treatment
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent prior to any study-specific procedures. * Men and women aged 18 or older. * Histologically or cytologically confirmed neoplasm causing pain and requiring management with opioids. * Self-reported active symptoms of OIC at screening (\<3 RFBMs/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 RFBMs/week on average aver the 2-week OIC confirmation period. * Receiving a stable maintenance opioid regimen consisting of a total daily dose of \>30 mg of oral morphine, or equianalgesic amount(s) of 1 or more opioid therapies for a minimum of 4 weeks prior to screening for cancer-related pain with no anticipated change in opioid dose requirement over the proposed study period as a result of disease progression.
Exclusion criteria
* Patients receiving Opioid regimen for treatment of pain other than related to cancer. * Any condition that may have affected the permeability of the blood-brain barrier, eg, known brain metastases, meningeal metastases, brain injury, multiple sclerosis, recent brain injury, uncontrolled epilepsy. * Patients with cancer-related pain due to ovarian cancer, leukaemia, or lymphoma are excluded. Patients with multiple myeloma will be allowed. * Patients requiring radiation therapy between the diaphragm and pelvis 4 weeks prior to Visit 1 (screening) and/or during Part A of the study are excluded. Any patients with suspected clinically relevant radiation-induced injury of small or large intestine are excluded. * Pregnancy or lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response (Responder/Non-responder) to Study Drug | Baseline to Week 4 | Response (responder/non-responder) to study drug, where a responder was defined as having at least 3 rescue-free bowel movements (RFBMs) per week during the 4-week Part A treatment period, with at least 1 RFBM per week increase over baseline for at least 3 out of 4 weeks. An RFBM was defined as a bowel movement (BM) without rescue laxatives in the previous 24 hours. |
Countries
Australia, Belgium, Bulgaria, Croatia, Czechia, Germany, Poland, Puerto Rico, Romania, Slovakia, South Africa, Spain, United Kingdom, United States
Participant flow
Recruitment details
This multicenter study was conducted in Poland, the Czech Republic, and the United States between 29 June 2011 and 20 September 2012. Due to recruitment challenges, enrollment to this study was stopped early and no new patients had been screened as of 20 April 2012. Fourteen patients were randomized across the 3 treatment groups.
Pre-assignment details
Part A was 8 weeks: 14-day screening period, 2-week OIC confirmation period, 4-week treatment period. Part B was 14 weeks: 12-week treatment period, 2-week follow-up period. Part B was optional for eligible patients completing Part A. NKTR-118 patients from Part A remained on the same NKTR-118 dose, while placebo patients received NKTR-118 25 mg.
Participants by arm
| Arm | Count |
|---|---|
| NKTR-118 12.5 mg NKTR-118 12.5 mg, oral treatment | 5 |
| NKTR-118 25 mg NKTR-118 25 mg, oral treatment | 5 |
| Placebo Placebo, oral treatment | 4 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part B | Severe non-compliance to protocol | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | NKTR-118 12.5 mg | NKTR-118 25 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 55.8 Years STANDARD_DEVIATION 9.2 | 53.8 Years STANDARD_DEVIATION 11.69 | 52.5 Years STANDARD_DEVIATION 4.93 | 54.1 Years STANDARD_DEVIATION 8.7 |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 3 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 5 | 3 / 5 | 3 / 4 | 1 / 3 | 5 / 6 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 4 | 0 / 3 | 0 / 6 |
Outcome results
Primary
Response (Responder/Non-responder) to Study Drug
Response (responder/non-responder) to study drug, where a responder was defined as having at least 3 rescue-free bowel movements (RFBMs) per week during the 4-week Part A treatment period, with at least 1 RFBM per week increase over baseline for at least 3 out of 4 weeks. An RFBM was defined as a bowel movement (BM) without rescue laxatives in the previous 24 hours.
Time frame: Baseline to Week 4
Population: All randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NKTR-118 12.5 mg | Response (Responder/Non-responder) to Study Drug | 4 Participants |
| NKTR-118 25 mg | Response (Responder/Non-responder) to Study Drug | 3 Participants |
| Placebo | Response (Responder/Non-responder) to Study Drug | 2 Participants |