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

NCT07038551 | Completed Phase 4

• 1 other identifier: 2024U0160
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 20

Brief 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

Conditions

Opioid-Induced Nausea and Vomitting(OINV)

Keywords

Nausea; Vomiting; Constipation

Outcome Measures

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.

  120 hours

Secondary Outcomes (19)

• 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)

  24, 48, 72, and 168 hours

• Change in nausea NRS from baseline

  Day 1, 2, 3, 5, and 7

• Average duration of nausea per day

  Day 1, 2, 3, 5, and 7

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

  24, 48, 72, 120, and 168 hours

• Proportion of patients who used rescue antiemetic medicines

  24, 48, 72, 120, and 168 hours

Study Arms (2)

Naldemedine

ACTIVE COMPARATOR

Drug: Naldemedine

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Naldemedine DRUG

over-encapsulated capsule of either 0.2 mg of naldemedine

Naldemedine

Placebo DRUG

over-encapsulated capsule of placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients who are 18 years of age or older at the time of obtaining consent
• Patients who can take oral medications, food, and beverages
• 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).
• Patients who are not expected to have a rapid change in their condition during the study period.
• Patients who can obtain written consent to participate in the study of their own will

You may not qualify if:

• Patients who have used opioid analgesics within 28 days prior to the date of consent
• Patients who have taken or are currently taking naldemedine
• Patients who have nausea and vomiting of CTCAE grade 2 or higher at the time of obtaining consent
• 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)
• 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.
• Pregnant or lactating patients
• Patients with suspected hypersensitivity to opioid receptor antagonists such as naldemedine, naltrexone, methylnaltrexone, and naloxone
• Patients with contraindications listed in the package inserts for naldemedine and opioid analgesics (tramadol, morphine, oxycodone, hydromorphone)
• Patients participating or scheduled to participate in clinical trials or other interventional studies
• Patients with gastrointestinal obstruction or suspected gastrointestinal obstruction, or patients with a history of gastrointestinal obstruction and a high risk of recurrence

Sponsors & Collaborators

• Shionogi: collaborator
• International University of Health and Welfare: lead

Study Sites (20)

Toyohashi municipal hospital

Toyohashi, Aichi-ken, Japan

Location

IUHW Narita Hospital

Narita, Chiba, Japan

Location

Iizuka Hospital

Iizuka, Fukuoka, Japan

Location

Hiroshima Prefectural Hospital

Hiroshima, Hiroshima, Japan

Location

Kansai Rosai Hospital

Amagasaki, Hyōgo, Japan

Location

National Hospital Organization HIMEJI M edical Center

Himeji, Hyōgo, Japan

Location

Hyogo Prefectural Nishinomiya Hospital

Nishinomiya, Hyōgo, Japan

Location

University of Tsukuba Hospital

Tsukuba, Ibaragi, Japan

Location

St. Marianna University School of Medicine

Kawasaki, Kanagawa, Japan

Location

Kanagawa Dental University Yokohama Clinic

Yokohama, Kanagawa, Japan

Location

Kyoto University Hospital

Kyoto, Kyoto, Japan

Location

Osaki Citizen Hospital

Ōsaki, Miyagi, Japan

Location

Kindai University Nara Hospital

Ikoma, Nara, Japan

Location

Niigata Cancer Center Hospital

Niigata, Niigata, Japan

Location

Beppu Medical Center

Beppu, Oita Prefecture, Japan

Location

Osaka Red Cross Hospital

Osaka, Osaka, Japan

Location

National Cancer Center Hospital

Chuo Ku, Tokyo, Japan

Location

Cancer Institute Hospital of Japanese Fo undation for Cancer Research

Tokyo, Tokyo, Japan

Location

Showa University Koto Toyosu Hospital

Tokyo, Tokyo, Japan

Location

Toyama University Hospital

Toyama, Toyama, Japan

Location

MeSH Terms

Conditions

Nausea; Vomiting; Constipation

Interventions

naldemedine

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Ph.D.

Study Record Dates

• First Submitted: June 18, 2025
• First Posted: June 26, 2025
• Study Start: June 20, 2025
• Primary Completion: February 13, 2026
• Study Completion: February 13, 2026
• Last Updated: June 3, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available beginning 6 months following publication of the primary results, with no end date.
• Access Criteria: Access to the IPD and supporting information will be granted to researchers who provide a scientifically and methodologically sound research proposal. The data to be accessed will include de-identified individual participant data underlying the primary and secondary outcomes of the study, including complete response rates (CR5, CR1, CR3, and CR7), nausea Numerical Rating Scale (NRS) scores, vomiting events, duration of nausea, and use of rescue antiemetic medications. The study protocol will also be available. Data will be made available upon submission of a research proposal to the corresponding investigator. Access will be granted following review and approval by the study team. Data will be shared after execution of a data sharing agreement, in accordance with institutional and ethical guidelines.

Locations

JP (20)