Opioid-Induced Constipation (OIC)
Conditions
Keywords
Non-Cancer-Related Pain, Opioid-Induced Constipation
Brief summary
The purpose of this study is to evaluate the long-term safety and tolerability of NKTR-118 treatment of opioid-induced constipation (OIC) in patients with non-cancer-related pain.
Interventions
DRUGNKTR-118
25 mg oral tablet once daily
DRUGUsual care
As prescribed by the investigator
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent prior to any study-specific procedures. * NEW PATIENTS ONLY: 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 the BMs over the previous 4 weeks); and Documented confirmed OIC (\<3 SBMs/week on average over the 2-week OIC confirmation period. * PATIENTS ENROLLING FROM OTHER NKTR-118 STUDIES: Receiving a stable maintenance opioid regimen consisting of a total daily dose of 30 mg to 1000 mg or oral morphine, or equianalgesic amount(s) of 1 or more opioid therapies. * FOR PATIENTS RANDOMIZED TO RECEIVE NKTR-118: Willingness to stop all laxatives and other bowel regimens including prune juice and herbal products throughout the 52-week treatment period, and to use only bisacodyl as rescue medication if 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 related to the gastrointestinal tract that could impose a risk to the patient. * Pregnancy or lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Patients Experiencing at Least One Adverse Event (AE) | Baseline (Week 0) to end of the follow-up period | The incidence of patients experiencing at least one AE during the randomized treatment and follow-up periods was calculated. |
| Incidence of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP) | Baseline (Week 0) to end of the follow-up period | The incidence of patients experiencing AEs that resulted in discontinuation of IP during the randomized treatment or follow-up periods was calculated. |
| Incidence of Patients Experiencing Severe Adverse Events (SAEs) | Baseline (Week 0) to end of the follow-up period | The incidence of patients experiencing SAEs during the randomized treatment and follow-up periods was calculated. |
Countries
United States
Participant flow
Recruitment details
This multicenter study was conducted in the United States between 18 April 2011 and 03 December 2012.
Pre-assignment details
The study duration was 54 to 58 weeks. New patients underwent an initial screening period lasting up to 2 weeks and a 2-week OIC confirmation period. New patients and patients enrolling from another study (also referred to as 'roll over patients') entered the 52-week treatment period, followed by a 2 week follow-up period.
Participants by arm
| Arm | Count |
|---|---|
| NKTR-118 25 mg NKTR-118 25 mg QD, oral treatment | 534 |
| Usual Care Laxative treatment regimen for OIC determined by the investigator according to his/her best clinical judgment. | 270 |
| Total | 804 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 56 | 6 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Did not receive treatment | 4 | 0 |
| Overall Study | Eligibility Criteria Not Fulfilled | 9 | 6 |
| Overall Study | Lack of Efficacy | 4 | 0 |
| Overall Study | Lost to Follow-up | 40 | 20 |
| Overall Study | Other | 22 | 9 |
| Overall Study | Severe noncompliance with protocol | 9 | 2 |
| Overall Study | Study-Specific Withdrawal Criteria | 16 | 7 |
| Overall Study | Withdrawal by Subject | 72 | 38 |
Baseline characteristics
| Characteristic | NKTR-118 25 mg | Usual Care | Total |
|---|---|---|---|
| Age, Continuous | 52.8 Years STANDARD_DEVIATION 10.09 | 52.7 Years STANDARD_DEVIATION 10.24 | 52.7 Years STANDARD_DEVIATION 10.13 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 98 Participants | 60 Participants | 158 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 423 Participants | 204 Participants | 627 Participants |
| Sex: Female, Male Female | 353 Participants | 179 Participants | 532 Participants |
| Sex: Female, Male Male | 181 Participants | 91 Participants | 272 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 365 / 534 | 152 / 270 |
| serious Total, serious adverse events | 51 / 534 | 30 / 270 |
Outcome results
Primary
Incidence of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP)
The incidence of patients experiencing AEs that resulted in discontinuation of IP during the randomized treatment or follow-up periods was calculated.
Time frame: Baseline (Week 0) to end of the follow-up period
Population: The Safety analysis set included all randomized patients who received at least 1 dose of IP and patients who received Usual Care, with the exception of patients who were randomized multiple times within the program at different centers or patients who were randomized at sites where data integrity issues were identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NKTR-118 25 mg | Incidence of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP) | 56 Participants |
| Usual Care | Incidence of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP) | NA Participants |
Primary
Incidence of Patients Experiencing at Least One Adverse Event (AE)
The incidence of patients experiencing at least one AE during the randomized treatment and follow-up periods was calculated.
Time frame: Baseline (Week 0) to end of the follow-up period
Population: The Safety analysis set included all randomized patients who received at least 1 dose of IP and patients who received Usual Care, with the exception of patients who were randomized multiple times within the program at different centers or patients who were randomized at sites where data integrity issues were identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NKTR-118 25 mg | Incidence of Patients Experiencing at Least One Adverse Event (AE) | 437 Participants |
| Usual Care | Incidence of Patients Experiencing at Least One Adverse Event (AE) | 195 Participants |
Primary
Incidence of Patients Experiencing Severe Adverse Events (SAEs)
The incidence of patients experiencing SAEs during the randomized treatment and follow-up periods was calculated.
Time frame: Baseline (Week 0) to end of the follow-up period
Population: The Safety analysis set included all randomized patients who received at least 1 dose of IP and patients who received Usual Care, with the exception of patients who were randomized multiple times within the program at different centers or patients who were randomized at sites where data integrity issues were identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NKTR-118 25 mg | Incidence of Patients Experiencing Severe Adverse Events (SAEs) | 51 Participants |
| Usual Care | Incidence of Patients Experiencing Severe Adverse Events (SAEs) | 30 Participants |