Opioid-induced constipation
Conditions
Interventions
Naldemedine Group:In Period 1: Naldemedine at a dose of 0.2 mg (naldemedine 0.2 mg tablet × 1) will be orally administered once daily for 14 days.
In Period 2: Naldemedine at a dose of 0.2 mg (naldeme
Placebo Group:In period 1: Placebo tablet matching the naldemedine 0.2 mg tablet will be orally administered once daily for 14 days.
In period 2: Naldemedine at a dose of 0.2 mg (naldemedine 0.2 mg ta
Sponsors
The Second Hospital of Anhui Medical University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Patients aged 18 years or older at the time of informed consent; 2. Men and women, inpatients and outpatients; 3. Patients with histologically or cytologically confirmed neoplasm causing pain and requiring treatment with opioids; 4. Patients who must have been treated with opioids (regular-use) for at least 2 weeks prior to the informed consent obtained, and be treated with a stable opioid regimen for 14 days prior to the first administration of IMP (100 to 200% of the dose of regular-use opioids on the day of 14 days prior to the first administration of IMP); 5. Patients who are currently receiving laxatives for OIC, or who had been treated with laxatives and are not currently receiving laxatives due to insufficient efficacy or other reasons; 6. Patients whose frequency of SBMs = 5 times during 14 consecutive days prior to the enrollment, and those who experience one or more of the following bowel symptoms in at least 25% of all bowel movements (BMs) regardless of using the rescue-use laxatives (a BM occurring within 24 hours after optional rescue-use laxative therapy will not be considered an SBM); -Straining during of BMs (2 [moderate] or above on the straining symptom score) -Feeling of incomplete evacuation -Passage of hard stools or pellets (1 or 2 on Bristol Stool Form Scale) 7. Patients who are able to receive oral intake of drugs, food and beverages; 8. Patients who are able to walk and carry out daily activities without assistance (0 to 2 on Performance Status [PS] of Eastern Cooperative Oncology Group [ECOG]) 9. Patients who are able to assess condition using the patient’s diary (if the patient is capable of assessment of patient's diary but cannot record the assessment on the patient's diary, recording by someone on behalf of the patient will be allowed); 10. Patients whose life expectance = 20 weeks; 11. Patients who are able to understand and willing to sign an informed consent form prior to the Screening Period, and comply with all study procedures and requirements.
Exclusion criteria
Exclusion criteria: 1. Patients who received a new cancer chemotherapy which had never been received previously, within 14 days prior to the informed consent obtained or during the Screening Period. 2. Patients who received a cancer chemotherapy which had been received previously and which is considered to have obvious effects on the gastrointestinal (GI) functions based on the treatment episodes, within 14 days prior to the informed consent obtained or during the Screening Period. 3. Patients who have evidence of significant structural abnormalities of the GI tract (such as mechanical ileus), active medical diseases affecting bowel transit (such as paralytic ileus, peritoneal metastasis or peritoneal cancer affecting GI function, uncontrolled hyperthyroidism or hypothyroidism), irritable bowel syndrome (IBS), inflammatory bowel disease (such as ulcerative colitis, Crohn's disease), or active diverticular disease, pelvic disorder which causes constipation (such as uterine prolapse, rectal prolapse, and uterine fibroids affecting bowel movement) , or these diseases which are considered to have obvious effects on the GI functions by the investigator/subinvestigator even if these diseases have recovered now. 4. Patients who underwent surgery, intervention (such as nerve block) or radiotherapy which is considered to have obvious effects on the GI functions within 28 days prior to the informed consent obtained or during the Screening Period, or who are scheduled to receive such surgery, intervention or radiotherapy. 5. Patients who are pregnant or lactating women, or who expect own pregnancy or partner’s pregnancy during the study period. 6. Patients who have evidence of ileus within 1 year prior to the informed consent obtained. 7. Patients who have never taken laxatives for the treatment of OIC 8. Patients who have history of any potential non-opioid cause of bowel dysfunction that may be a major contributor to the constipation. 9. Patients who have reported no bowel movements for 7 consecutive days prior to the registration for the Treatment Period. 10. Abnormal laboratory tests within 7 days prior to the enrollment in the Treatment Period: a. >2 × upper limit of normal (ULN) for alanine aminotransferase (ALT) or aspartate aminotransferase (AST) b. >1.5 × ULN for total bilirubin c. >1.5 × ULN for serum creatinine 11. Patients who had fecal disimpaction during the Screening Period. 12. Patients with colostomy. 13. Patients who were found to have medically significant cardiovascular (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident), respiratory, hepatic, or renal functional disorders and metabolic dysfunction from the medical history, spinal cord compression or vertebral metastasis, laboratory tests, electrocardiorapm (ECG), and physical findings, and who were considered ineligible for the study by the investigator/subinvestigator. 14. Patients who are known or suspected to have hypersensitivity to naldemedine, naltrexone, methylnaltrexone, naloxone, or any other opioid antagonist. 15. Patients who are currently receiving opioid receptor antagonists or partial agonists, or who are scheduled to receive such medicine by the completion of the Treatment Period 16. Patients who have received any other study drug within 28 days prior to the informed consent obtained (including the study drugs intended for obtaining a marketing approval). 17. Patients who have participated in naldemedine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of SBM responders during Period 1 of the Treatment Period. An SBM responder is defined as a subject with 3 or more spontaneous bowel movements (SBMs) per week and an increase of 1 or more SBM per week from baseline. ; | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects with CSBM (Complete Spontaneous Bowel Movement) responders during the Treatment Period. A CSBM responder is defined as a subject with SBM accompanied by feeling of complete evacuation.;Proportion of subjects with SBM/CSBM responder for each week during the Treatment Period.;Change in the frequency of SBMs/CSBMs per week from baseline during the Treatment Period.;Weekly change in frequency of SBMs/CSBMs per week from baseline during the Treatment Period.;Time to the first SBM/CSBM after the first administration of (investigational medicinal product) IMP.;Daily Change in the frequency of SBMs from baseline during the Treatment Period.;Change in the number of Days with at least 1 SBM/CSBM per week from baseline during the Treatment Period.;Proportion of subjects with at least 1 SBM/ CSBM for each observation time period within 24 hours after the first administration of IMP during the Treatment Period.;Change in the frequency of SBMs with Bristol Stool Scale (BSS) score of 3 or 4 per week from baseline during the Treatment Period.;Change in the frequency of SBMs per week without straining (straining score of 0 or 1 during bowel movement) from baseline during the Treatment Period.;Change in the frequency of rescue-use laxatives per week from baseline during the Treatment Period. ;Weekly Change in the abdominal bloating and abdominal discomfort scores from baseline during the Treatment Period.;Change in Subject Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) from baseline to each observation time point.;Proportion of subjects with PAC-SYM/PAC-QOL responder. A PAC-SYM / PAC-QOL responder is defined as a subject with an increase of 1 or more in overall for PAC-SYM (or in a domain for satisfaction of PAC-QOL) per week from baseline.;Change in the time of spending at toilet for defecation from baseline during the Treatment Period.;Change in the number of dishes for each meal and the numbe | — |
Countries
China
Contacts
Public ContactChen Zhendong / Zhang Mingjun
The Second Hospital of Anhui Medical University
Outcome results
None listed