Opioid-Induced Nausea and Vomitting(OINV)Phase 4NCT07038551
Prophylactic Use of Naldemedine on Opioid-induced Nausea and Vomiting in Patients With Cancer: POSEIDON Study
A Phase 4 study testing Naldemedine in people with Opioid-Induced Nausea and Vomitting(OINV), run by International University of Health and Welfare at 20 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Opioid-Induced Nausea and Vomitting(OINV)
- What is being tested?
- Naldemedine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 20 sitesJapan
- Study dates
- 20 Jun 2025to 13 Feb 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 21Show fewer
- 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
- 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
- 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
- Patients with symptomatic intracranial conditions (such as brain metastases or leptomeningeal disease)
- Patients with suspected dysfunction or impairment of the blood-brain barrier
- Patients for whom it is difficult to explain the contents of the study or obtain consent due to cognitive impairment or psychiatric illness
- 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
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
Japan20 sites
Kansai Rosai Hospital
Amagasaki, Hyōgo
Beppu Medical Center
Beppu, Oita Prefecture
National Cancer Center Hospital
Chuo Ku, Tokyo
National Hospital Organization HIMEJI M edical Center
Himeji, Hyōgo
Hiroshima Prefectural Hospital
Hiroshima, Hiroshima
Iizuka Hospital
Iizuka, Fukuoka
Kindai University Nara Hospital
Ikoma, Nara
St. Marianna University School of Medicine
Kawasaki, Kanagawa
Kyoto University Hospital
Kyoto, Kyoto
IUHW Narita Hospital
Narita, Chiba
Niigata Cancer Center Hospital
Niigata, Niigata
Hyogo Prefectural Nishinomiya Hospital
Nishinomiya, Hyōgo
Osaka Red Cross Hospital
Osaka, Osaka
Osaki Citizen Hospital
Ōsaki, Miyagi
Cancer Institute Hospital of Japanese Fo undation for Cancer Research
Tokyo, Tokyo
Showa University Koto Toyosu Hospital
Tokyo, Tokyo
Toyama University Hospital
Toyama, Toyama
Toyohashi municipal hospital
Toyohashi, Aichi-ken
University of Tsukuba Hospital
Tsukuba, Ibaragi
Kanagawa Dental University Yokohama Clinic
Yokohama, Kanagawa
About this study
Official title: Prophylactic Use of Naldemedine on Opioid-Induced Nausea and Vomiting in Patients With Cancer: A Multicenter, Randomized, Placebo-Controlled, Double-Blind Study
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
- Being tested
- Naldemedine, Placebo
- Keywords
- Nausea, Vomiting, Constipation
- Medical subject headings
- Nausea, Vomiting, Constipation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaldemedineDrug
over-encapsulated capsule of either 0.2 mg of naldemedine
PlaceboDrug
over-encapsulated capsule of placebo
| Study group | Role | What they receive |
|---|---|---|
| Naldemedine | Active comparator | Not described Receives: Drug: Naldemedine |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 24, 48, 72, and 168 hours
Change in nausea NRS from baseline
nausea NRS[0-10]: Higher scores indicate greater nausea intensity
Measured: Day 1, 2, 3, 5, and 7
Average duration of nausea per day
Measured: Day 1, 2, 3, 5, and 7
Proportion of patients who vomited at least once after starting opioid analgesics
Measured: 24, 48, 72, 120, and 168 hours
Proportion of patients who used rescue antiemetic medicines
Measured: 24, 48, 72, 120, and 168 hours
Number of times rescue antiemetic medicines were used
Measured: 24, 48, 72, 120, and 168 hours
Proportion of patients with Spontaneous Bowel Movement (SBM: spontaneous bowel movement) of 3 or more per week
Measured: 7days
Proportion of patients with Spontaneous Bowel Movement (CSBM: SBM without sensation of incomplete evacuation) of 3 or more per week
Measured: 7days
Proportion of patients experiencing a sensation of incomplete evacuation in 25% or more of defecation
Measured: 7days
Proportion of patients with SBM without straining of 3 or more per week
Measured: 7days
Proportion of patients experiencing a sensation of straining in 25% or more of defecation
Measured: 7days
Proportion of patients with SBM without sensation of straining or sensation of incomplete evacuation of 3 or more per week
Measured: 7days
Proportion of patients experiencing a sensation of straining or sensation of incomplete evacuation in 25% or more of defecation
Measured: 7days
Number of times rescue laxatives or enema or digital evacuation were used
Measured: 7days
Proportion of patients with a Bowel Function Index of less than 28.8
Measured: 7days
Change in Bowel Function Index from baseline
Measured: 7-11days
the percentage of patients whose satisfaction worsened
Measured: 7-11days
Change in Global Quality of Life score and scores for each subscale evaluation of the EORTC-QLQ-C15 PAL
Measured: 7-11days
Change in pain NRS from baseline
pain NRS[0-10]: Higher scores indicate greater pain intensity
Measured: 1,2,3,5,7days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2025
- Study start20 Jun 2025
- Primary completion13 Feb 2026
- Study completion13 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid-Induced Nausea and Vomitting(OINV)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- International University of Health and Welfare
- Sponsor type
- University, hospital or other
- Collaborators
- Shionogi
- Responsible party
- Principal investigator, Takaomi Kessoku, International University of Health and Welfare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07038551
- Sponsor's protocol ID
- 2024U0160
- Status last verified
- May 2026
- First submitted
- 18 Jun 2025
- Last updated
- 3 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
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
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prophylactic Use of Naldemedine on Opioid-Induced Nausea and Vomiting in Patients With Cancer: A Multicenter, Randomized, Placebo-Controlled, Double-Blind Study
- ClinicalTrials.gov ID
- NCT07038551
- Acronym / sponsor ID
- 2024U0160
- Keywords
- Nausea, Vomiting, Constipation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- International University of Health and WelfareUniversity, hospital or other
- Collaborators
- Shionogi
- Study start
- 20 Jun 2025 (actual)
- Primary completion
- 13 Feb 2026 (actual)
- Study completion
- 13 Feb 2026 (actual)
- First posted
- 26 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Naldemedine | Active comparator | Drug: Naldemedine |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (21 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Naldemedineover-encapsulated capsule of either 0.2 mg of naldemedine | Drug | Naldemedine |
| Placeboover-encapsulated capsule of placebo | Drug | Placebo |
Primary outcome
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
19 secondary outcomes
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
Change in nausea NRS from baseline
Time frame: Day 1, 2, 3, 5, and 7
Average duration of nausea per day
Time frame: Day 1, 2, 3, 5, and 7
Proportion of patients who vomited at least once after starting opioid analgesics
Time frame: 24, 48, 72, 120, and 168 hours
Proportion of patients who used rescue antiemetic medicines
Time frame: 24, 48, 72, 120, and 168 hours
Number of times rescue antiemetic medicines were used
Time frame: 24, 48, 72, 120, and 168 hours
Proportion of patients with Spontaneous Bowel Movement (SBM: spontaneous bowel movement) of 3 or more per week
Time frame: 7days
Proportion of patients with Spontaneous Bowel Movement (CSBM: SBM without sensation of incomplete evacuation) of 3 or more per week
Time frame: 7days
Proportion of patients experiencing a sensation of incomplete evacuation in 25% or more of defecation
Time frame: 7days
Proportion of patients with SBM without straining of 3 or more per week
Time frame: 7days
Proportion of patients experiencing a sensation of straining in 25% or more of defecation
Time frame: 7days
Proportion of patients with SBM without sensation of straining or sensation of incomplete evacuation of 3 or more per week
Time frame: 7days
Proportion of patients experiencing a sensation of straining or sensation of incomplete evacuation in 25% or more of defecation
Time frame: 7days
Number of times rescue laxatives or enema or digital evacuation were used
Time frame: 7days
Proportion of patients with a Bowel Function Index of less than 28.8
Time frame: 7days
Change in Bowel Function Index from baseline
Time frame: 7-11days
the percentage of patients whose satisfaction worsened
Time frame: 7-11days
Change in Global Quality of Life score and scores for each subscale evaluation of the EORTC-QLQ-C15 PAL
Time frame: 7-11days
Change in pain NRS from baseline
Time frame: 1,2,3,5,7days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2026.
- Derived from this study: PubMed 42468954Ishihara 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.
- Individual participant dataSharing planned: 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Naldemedine in people with Opioid-Induced Nausea and Vomitting(OINV), run by International University of Health and Welfare at 20 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07038551, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2026.