A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of the Preventive Effect of Naldemedine on Opioid-Induced Constipation

JRCT ID: jRCTs031200397

Registered date:05/03/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: neoplasms
• Date of first enrollment: 05/03/2021
• Target sample size: 100
• Study type: Interventional
• Intervention(s): Patients who meet the patient eligibility and exclusion criteria and give consent will be randomly assigned to the naldemedine group (Symproic 0.2 mg) or placebo group. The study evaluation period will be 14 days after the start of naldemedine (or placebo), and the naldemedine group will take Symproic 0.2 mg once a day after breakfast for 14 days. On the other hand, the placebo group will take placebo once a day after breakfast for 14 days. However, the first dose will be given orally at the time of the first oral administration of strong opioids, not only after breakfast.

Outcome(s)

• Primary Outcome: Percentage of patients with a Bowel Function Index of less than 28.8 on Day 14

Secondary Outcome

1)Percentage of patients with a Bowel Function Index of less than 28.8 on Day 7
2) Amount and rate of change in Bowel Function Index from Day 1 on Day 7 and 14
3) Percentage and number of patients with Spontaneous Bowel Movement of 3 or more per week on Day 7 and 14
4) Percentage and number of patients with Complete Spontaneous Bowel Movement (CSBM: spontaneous bowel movement without urgency or residual defecation) of 3 or more per week on Days 7 and 14
5) Bowel movements during defecation (yes/no), squeezing during each defecation (not at all/just a little/moderately/quite a lot/very much), residual feeling during each defecation (yes/no)
6) Overall bowel movements (4 levels: dissatisfied, somewhat dissatisfied, somewhat satisfied, satisfied) in the last week on Day 1, 7, and 14, and changes in bowel movements between Day 1 and Day 7 and between Day 1 and Day 14
7) PAC-SYM and PAC-QOL for Day 1 and 14
8) EORTC QLQ-C15-PAL, and subscale scores for Day 1, 7, and 14
9) EORTC QLQ-C15-PAL item 10 (constipation) for Day 1, 7, and 14, with the percentages of patients who responded "a little," "a lot," "a great deal," and "a lot" or "a great deal
10) Amount of change in JPAC-QOL for Day 1 and 14
11) Amount of change in JPAC-SYM on Day 1 and 14
12) Percentage of patients who vomited at least once during the 3 days from Day 1 to Day 3
13) Percentage of patients who used antiemetic drugs during the 3 days from Day 1 to Day 3
14) Percentage of patients who responded "a little", "a lot", "very much", and "a lot" or "very much" to EORTC QLQ-C15-PAL item 9 (nausea) on Days 1, 7, and 14
15) Number of times rescue laxatives were used
16) Number of episodes of diarrhea that occurred during administration of the study drug
17) Adverse events that occurred during study drug administration
18) Double-blind validation

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Cancer patients who are starting regular oral use of strong opioids (morphine, oxycodone,
hydromorphone) for the first time for cancer pain
2) Age 20 years or older (at the time of obtaining consent)
3) Patients who are able to take oral medications, food, and beverages
4) Patients who are considered capable of self-recording in the patient diary (proxy recording in the patient
diary is acceptable if the patient is capable of self-assessment).
5) Patients who are not expected to have a rapid change in their cancer condition during the study period.
6) Patients who have received sufficient explanation and written consent of their own free will to participate
in this study.

Exclude criteria

1) Patients with gastrointestinal obstruction or suspected gastrointestinal obstruction, or patients with
a history of gastrointestinal obstruction and a high risk of recurrence
2) Patients who have undergone surgery, radiotherapy, or procedures affecting gastrointestinal function
(e.g., nerve block) within 14 days prior to the date of enrollment, or who are scheduled to undergo such
procedures during the study period.
3) Patients with medically significant cardiovascular, respiratory, hepatic, or renal dysfunction based on
history, clinical laboratory values, electrocardiogram, or physical examination, who are judged inappropriate to participate in the study.
4) Patients who have received or are currently receiving naldemedine medication
5) Patients who have had severe diarrhea (more than 7 times a day) or who have had a stool extraction for constipation within the past 7 days
6) Patients who have used opioid patches or injectable opioids in the past 7 days.
7) Patients who have received cancer drug therapy that is certain to affect defecation within 14 days prior to the initial enrollment date, or who are scheduled to receive such therapy within the study period. Cancer
drug therapy that is certain to affect defecation will be defined as follows.
1.Initial administration of a therapeutic regimen containing irinotecan (CPT-11)
2.Other cancer drug therapy that is considered certain to affect defecation.
However, the following cases may be considered as not affecting defecation
a) Chemotherapy with the same regimen as the previous course or chemotherapy with the same drug and
dose, and there was no moderate or greater constipation or diarrhea (CTCAE v5.0 Grade 2 or higher)
during the previous course or previous chemotherapy.
b) Patients who have received oral anticancer agents (e.g. TS-1) daily and have not had moderate or severe constipation or diarrhea (CTCAE v5.0 Grade 2 or higher) for at least 1 week from the start of oral
chemotherapy to the start of study drug.
8) Pregnant or lactating patients
9) Patients with suspected hypersensitivity to opioid receptor antagonists such as naldemedine, naltrexone, methylnaltrexone, and naloxone.
10) Other patients who are judged by the principal investigator or sub-investigator to be inappropriate for
participation in the study based on concomitant therapy or medical findings.

Related Information

• Primary Sponsor: Jun Hamano
• Source(s) of Monetary Support: Japanese Society for Palliative Medicine