Constipation
Conditions
Keywords
Cancer, Constipation, Opioid
Brief summary
The purpose of this study is to compare the effect of naloxegol versus the patient's usual care in treating opioid-induced constipation, as well as the effect on the patient's quality of life and how much pain is experienced. Also, the purpose of this study is to compare whether treatment with naloxegol versus usual care has any impact on the number of hospital or clinic visits or telephone calls to the patient's physician that are related to constipation, and to determine the patient's preference for continuing to receive naloxegol as treatment for opioid-induced constipation.
Detailed description
Opioid-induced constipation (OIC) is a common symptom in patients with cancer-related pain and requires burdensome self-titration of laxatives for prophylaxis and treatment. Consequently, naloxegol may have an important role in this setting. Naloxegol has been evaluated in relieving OIC with cancer patients in a randomized, double blind, placebo-controlled trial over 4 weeks with a 12-week extension phase. However, accrual was challenging and the trial was closed early. Given the complexity of cancer and its treatment, a key first step is to determine if evaluating naloxegol versus standard of care is feasible in the management of OIC in this setting. Subjects will receive naloxegol 25mg daily or usual care for a 2-week initial treatment period followed by 3-day washout period, then a 2-week crossover treatment period where subjects will receive naloxegol or usual care. Treatment assignment during the initial and crossover treatment periods will be dictated by the randomization arm. Subjects will also have the option to participate in a 12-week extension phase of naloxegol.
Interventions
DRUGnaloxegol
Sponsors
AstraZeneca
Joseph Ma
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults greater than or equal to 18 years old. * Eastern Cooperative Oncology Group (ECOG) less than or equal to 3. * Glomerular filtration rate (GFR) greater than or equal to 30 ml/min/1.73m2 by Modification of Diet in Renal Disease (MDRD). * Corrected serum calcium level less than or equal to 10.5 mg/dL. * Estimated life expectancy greater than or equal to 6 months. * Negative pregnancy test prior to initiating study treatment for females of childbearing potential.
Exclusion criteria
* Patients receiving the following medications within 3 days of Study Day 1 and/or are planned to receive throughout the duration of the study period: opioid antagonist, mixed antagonist, a strong CYP3A4 and/or P-glycoprotein (P-gp) inhibitor, a moderate CYP3A4 and/or P-gp inhibitor, and/or a strong CYP3A4 inducer. * Concurrent total parenteral nutrition and/or use of metoclopramide. * Patients at high risk for bowel perforation. * Constipation that was not primarily caused by opioids in the investigator's medical opinion. * A condition that may have affected the permeability of the blood-brain barrier (e.g., known brain metastases, meningeal metastases, brain injury, multiple sclerosis, recent brain injury, uncontrolled epilepsy) * Patient has clinically active diverticular disease. * Past medical history of irritable bowel syndrome, signs of active gastrointestinal (GI) bleeding, acute surgical abdomen, bowel stents, indwelling peritoneal catheter, mechanical GI obstruction, fecal impaction, or fecal ostomy. * Patient has motility/neurologic disorders including autonomic failure (spinal cord lesions, tumor invasion of nerves) and/or poorly controlled endocrine/metabolic disorders (hypercalcemia, hypokalemia, diabetes, hypothyroidism), as determined by the investigator. * Uncontrolled cancer pain despite analgesic therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Completed Naloxegol 25mg and the Number of Participants That Completed Standard of Care | 4 weeks | completion of treatment defined as participants receiving all single daily doses for 2 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A- Naloxegol/Standard of Care Patients in Arm A will receive a single daily dose of 25mg naloxegol for the 2-week initial treatment period, followed by a 3-day washout period and 2-week crossover treatment period in which the patient will receive the treating physician's usual care for OIC using a stimulant laxative + rescue medication.
naloxegol | 4 |
| B - Standard of Care/Naloxegol Patients in Arm B will receive the treating physician's usual care for OIC using a stimulant laxative + rescue medication for the 2-week initial treatment period, followed by a 3-day washout period and 2-week crossover period in which the patient will receive a single daily dose of 25mg naloxegol.
naloxegol | 3 |
| Total | 7 |
Baseline characteristics
| Characteristic | A- Naloxegol/Standard of Care | B - Standard of Care/Naloxegol | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 7 Participants |
| Region of Enrollment United States | 4 participants | 3 participants | 7 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 5 | 0 / 4 |
| other Total, other adverse events | 3 / 5 | 2 / 4 |
| serious Total, serious adverse events | 3 / 5 | 1 / 4 |
Outcome results
Primary
Number of Participants That Completed Naloxegol 25mg and the Number of Participants That Completed Standard of Care
completion of treatment defined as participants receiving all single daily doses for 2 weeks
Time frame: 4 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A (Naloxegol/Standard of Care) | Number of Participants That Completed Naloxegol 25mg and the Number of Participants That Completed Standard of Care | Naloxegol | 4 Participants |
| Arm A (Naloxegol/Standard of Care) | Number of Participants That Completed Naloxegol 25mg and the Number of Participants That Completed Standard of Care | Standard of Care | 1 Participants |
| Arm B (Standard of Care/ Naloxego) | Number of Participants That Completed Naloxegol 25mg and the Number of Participants That Completed Standard of Care | Naloxegol | 3 Participants |
| Arm B (Standard of Care/ Naloxego) | Number of Participants That Completed Naloxegol 25mg and the Number of Participants That Completed Standard of Care | Standard of Care | 1 Participants |