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CompletedNCT07038551Updated Jun 3, 2026

Prophylactic Use of Naldemedine on Opioid-induced Nausea and Vomiting in Patients With Cancer: POSEIDON Study

A Phase 4 interventional study of Naldemedine and Placebo in Opioid-Induced Nausea and Vomitting(OINV), sponsored by International University of Health and Welfare. Completed at 20 sites in Japan. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-03.

Sponsored by International University of Health and Welfare · Phase 4, Interventional, and Prevention

Phase
Phase 4
Study type
Interventional
Enrollment
120
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Opioid analgesics can cause side effects such as constipation, nausea, and vomiting by acting on opioid receptors widely distributed in the peripheral nervous system. This can sometimes make it difficult to achieve and maintain pain relief and continue pain treatment. Among these side effects, nausea and vomiting are specifically referred to as opioid-induced nausea and vomiting (OINV). OINV is known to occur during the initial administration or dose escalation of opioid analgesics, and it not only decreases the quality of life for patients but also reduces adherence to opioid analgesics, which can have a negative impact on pain management. Therefore, appropriate management is crucial.

While the administration of conventional antiemetic drugs is recommended for the treatment of OINV, there is a lack of high-quality studies evaluating their effectiveness, and studies comparing treatment effects with a placebo have not been reported.

The objective is to verify the effectiveness of naldemedine in preventing OINV in patients starting opioid analgesics for cancer

02

Conditions studied

  • Opioid-Induced Nausea and Vomitting(OINV)

Keywords

  • Nausea
  • Vomiting
  • Constipation
03

In context

Nausea

822 studies on the registry are indexed under Nausea; 104 are open to participants now.

This study's enrollment of 120 is close to the median of 115 across 703 interventional studies indexed under Nausea.

Browse Nausea studies →

Lead sponsor

International University of Health and Welfare is the lead sponsor of 4 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Patients who can be expected to initiate regular administration of opioid analgesics (tramadol, morphine, oxycodone, hydromorphone) for cancer pain and continue for 7 days or more.
  2. Patients who are 18 years of age or older at the time of obtaining consent
  3. Patients who can take oral medications, food, and beverages
  4. Patients who are considered capable of self-recording in the patient's diary (proxy recording in the patient's diary is acceptable if the patients are capable of self-assessment).
  5. Patients who are not expected to have a rapid change in their condition during the study period.
  6. Patients who can obtain written consent to participate in the study of their own will

Exclusion criteria

Exclusion Criteria:

  1. Patients who have used opioid analgesics within 28 days prior to the date of consent
  2. Patients who have taken or are currently taking naldemedine
  3. Patients who have nausea and vomiting of CTCAE grade 2 or higher at the time of obtaining consent
  4. Patients who have taken the following antiemetic drugs within 7 days prior to the date of consent Metoclopramide, domperidone, H1 histamine receptor antagonists, phenothiazine antipsychotics (chlorpromazine, levomepromazine, prochlorperazine), haloperidol, atypical antipsychotics (perospirone, risperidone, olanzapine), serotonin 5HT3 receptor antagonists (ondansetron, granisetron, ramosetron, palonosetron), corticosteroids (dexamethasone), scopolamine hydrobromide, NK1 receptor antagonists (aprepitant, fosaprepitant, fosnetupitant)

  5. Patients who have received cancer chemotherapy that is certain to affect nausea and vomiting within 14 days prior to the date of consent or who are scheduled to receive such therapy within the study period. Cancer chemotherapy that is certain to affect nausea and vomiting will be defined as follows:

    ① Initial administration of a therapeutic regimen containing irinotecan (CPT-11)

    ② Other cancer chemotherapy that is considered certain to affect nausea and vomiting.

    However, the following cases may be considered as not affecting defecation

    • Chemotherapy with the same regimen as the previous course or chemotherapy with the same drug and dose, and there was no moderate or greater nausea and vomiting (CTCAE v5.0 Grade 2 or higher) during the previous course or previous chemotherapy.
    • Patients who have received oral anticancer agents (e.g. TS-1) daily and have not had moderate or severe nausea and vomiting (CTCAE v5.0 Grade 2 or higher) for at least 1 week from the start of oral chemotherapy to the date of consent.
  6. Pregnant or lactating patients
  7. Patients with suspected hypersensitivity to opioid receptor antagonists such as naldemedine, naltrexone, methylnaltrexone, and naloxone
  8. Patients with contraindications listed in the package inserts for naldemedine and opioid analgesics (tramadol, morphine, oxycodone, hydromorphone)
  9. Patients participating or scheduled to participate in clinical trials or other interventional studies
  10. Patients with gastrointestinal obstruction or suspected gastrointestinal obstruction, or patients with a history of gastrointestinal obstruction and a high risk of recurrence
  11. Patients who have undergone surgery or treatment (e.g., nerve block) that affects gastrointestinal function, or radiation therapy to the head, intestinal tract, or pelvis within 14 days prior to the date of consent acquisition, or patients who are scheduled to undergo such treatment during the observation period
  12. 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
  13. Patients with symptomatic intracranial conditions (such as brain metastases or leptomeningeal disease)
  14. Patients with suspected dysfunction or impairment of the blood-brain barrier
  15. Patients for whom it is difficult to explain the contents of the study or obtain consent due to cognitive impairment or psychiatric illness
  16. Patients who are judged by the principal investigator or sub-investigator to be inappropriate to participate in this study based on other concomitant therapies or medical findings
05

Study design

Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
120 participants (actual)

Study arms

  • Active comparator
    Naldemedine

    Drug: Naldemedine

  • Placebo comparator
    Placebo

    Drug: Placebo

Interventions

  • DrugNaldemedine

    over-encapsulated capsule of either 0.2 mg of naldemedine

  • DrugPlacebo

    over-encapsulated capsule of placebo

06

What researchers measure

Primary outcomes

  1. The proportion of patients who achieved a Complete Response on Day 5 (CR5), defined as no vomiting up to 120 hours after starting opioid analgesic and no use of rescue antiemetic medications.

    Time frame: 120 hours

Secondary outcomes

  1. The proportion of patients who achieved a Complete Response at CR1, CR2, CR3, and CR7 (defined as no vomiting up to 24, 48, 72, and 168 hours after starting opioid analgesics, respectively, and no use of rescue antiemetic medications)

    Time frame: 24, 48, 72, and 168 hours

  2. Change in nausea NRS from baseline

    nausea NRS\[0-10\]: Higher scores indicate greater nausea intensity

    Time frame: Day 1, 2, 3, 5, and 7

  3. Average duration of nausea per day

    Time frame: Day 1, 2, 3, 5, and 7

  4. Proportion of patients who vomited at least once after starting opioid analgesics

    Time frame: 24, 48, 72, 120, and 168 hours

  5. Proportion of patients who used rescue antiemetic medicines

    Time frame: 24, 48, 72, 120, and 168 hours

  6. Number of times rescue antiemetic medicines were used

    Time frame: 24, 48, 72, 120, and 168 hours

  7. Proportion of patients with Spontaneous Bowel Movement (SBM: spontaneous bowel movement) of 3 or more per week

    Time frame: 7days

  8. Proportion of patients with Spontaneous Bowel Movement (CSBM: SBM without sensation of incomplete evacuation) of 3 or more per week

    Time frame: 7days

  9. Proportion of patients experiencing a sensation of incomplete evacuation in 25% or more of defecation

    Time frame: 7days

  10. Proportion of patients with SBM without straining of 3 or more per week

    Time frame: 7days

  11. Proportion of patients experiencing a sensation of straining in 25% or more of defecation

    Time frame: 7days

  12. Proportion of patients with SBM without sensation of straining or sensation of incomplete evacuation of 3 or more per week

    Time frame: 7days

  13. Proportion of patients experiencing a sensation of straining or sensation of incomplete evacuation in 25% or more of defecation

    Time frame: 7days

  14. Number of times rescue laxatives or enema or digital evacuation were used

    Time frame: 7days

  15. Proportion of patients with a Bowel Function Index of less than 28.8

    Time frame: 7days

  16. Change in Bowel Function Index from baseline

    Time frame: 7-11days

  17. the percentage of patients whose satisfaction worsened

    Time frame: 7-11days

  18. Change in Global Quality of Life score and scores for each subscale evaluation of the EORTC-QLQ-C15 PAL

    Time frame: 7-11days

  19. Change in pain NRS from baseline

    pain NRS\[0-10\]: Higher scores indicate greater pain intensity

    Time frame: 1,2,3,5,7days

07

Study locations

20 sites
  • Toyohashi municipal hospital
    Toyohashi, Aichi-ken, Japan
  • IUHW Narita Hospital
    Narita, Chiba, Japan
  • Iizuka Hospital
    Iizuka, Fukuoka, Japan
  • Hiroshima Prefectural Hospital
    Hiroshima, Hiroshima, Japan
  • Kansai Rosai Hospital
    Amagasaki, Hyōgo, Japan
  • National Hospital Organization HIMEJI M edical Center
    Himeji, Hyōgo, Japan
  • Hyogo Prefectural Nishinomiya Hospital
    Nishinomiya, Hyōgo, Japan
  • University of Tsukuba Hospital
    Tsukuba, Ibaragi, Japan
  • St. Marianna University School of Medicine
    Kawasaki, Kanagawa, Japan
  • Kanagawa Dental University Yokohama Clinic
    Yokohama, Kanagawa, Japan
  • Kyoto University Hospital
    Kyoto, Kyoto, Japan
  • Osaki Citizen Hospital
    Ōsaki, Miyagi, Japan
  • Kindai University Nara Hospital
    Ikoma, Nara, Japan
  • Niigata Cancer Center Hospital
    Niigata, Niigata, Japan
  • Beppu Medical Center
    Beppu, Oita Prefecture, Japan
  • Osaka Red Cross Hospital
    Osaka, Osaka, Japan
  • National Cancer Center Hospital
    Chuo Ku, Tokyo, Japan
  • Cancer Institute Hospital of Japanese Fo undation for Cancer Research
    Tokyo, Tokyo, Japan
  • Showa University Koto Toyosu Hospital
    Tokyo, Tokyo, Japan
  • Toyama University Hospital
    Toyama, Toyama, Japan
08

References and documents

Publications

  • Ishihara Y, Ohira M, Hokabe M, Yoshino S, Iwashita K, Takahashi K, Tomita N, Uneno Y, Kataoka S, Kurihashi T, Satomi E, Hamano J, Higashibata T, Kosugi K, Hirakawa M, Kajiura S, Ogihara S, Kida M, Morita T, Koretaka Y, Sonoyama T, Oyamada S, Nakajima A, Kessoku T. Multicentre, double-blind, randomised, placebo-controlled study on the prophylactic use of naldemedine for opioid-induced nausea and vomiting in patients with cancer (POSEIDON study): a protocol paper. BMJ Open. 2026 Jul 17;16(7):e114092. doi: 10.1136/bmjopen-2025-114092. PubMed 42468954 ↗

Individual participant data

Plan to share: Yes — De-identified individual participant data (IPD) underlying the results reported in this study will be shared. These data will include those related to the primary outcome (complete response within 120 hours \[CR5\]) as well as secondary outcomes, including complete response rates at different time points (CR1, CR3, and CR7), nausea Numerical Rating Scale (NRS) scores, vomiting events, and use of rescue medications.

Supporting information: Study protocol

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 3, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07038551
Lead sponsor
International University of Health and Welfare
Collaborators
Shionogi
Responsible party
Takaomi Kessoku (M.D., Ph.D., International University of Health and Welfare) — Principal investigator
First posted
Jun 26, 2025
Start date
Jun 20, 2025
Primary completion
Feb 13, 2026
Completion
Feb 13, 2026
Last update
Jun 3, 2026

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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