Opioid Induced Bowel DysfunctionPhase 2NCT01122030
Study to Evaluate the Safety and Efficacy of Naldemedine (S-297995) for the Treatment of Opioid-Induced Bowel Dysfunction in Subjects With Chronic Pain
A Phase 2 study testing Naldemedine in people with Opioid Induced Bowel Dysfunction, run by Shionogi at 1 site in United States.
Trial summary
The primary objective of the study is to evaluate the safety of single doses of oral naldemedine in adults physically dependent on opioids. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid Induced Bowel Dysfunction
- 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
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 19 May 2010to 22 Mar 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Understand and sign an informed consent form
- Males will agree to use an approved double-barrier method of contraception from Day 1 until 1 month after study completion
- Subject tests negative on urine drug test unless the subject has a prescription for the drug(s) that test positive
Who cannot join
- Subjects under opioid therapy for cancer-related pain or for the management of drug addiction
- Fecal incontinence, irritable bowel syndrome, inflammatory bowel disease, or other active medical disorders associated with diarrhea, intermittent loose stools, or constipation
- Subjects who have participated in any other investigational drug study within 30 days prior to Day 1
- Prior exposure to S-297995
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety and Efficacy of S-297995 for the Treatment of Opioid-Induced Bowel Dysfunction in Subjects With Chronic Pain
The primary objective of the study is to evaluate the safety of single doses of oral naldemedine in adults physically dependent on opioids.
Read the detailed description
A single dose of naldemedine or matching placebo will be administered orally to each cohort of 12 participants (9 treatments, 3 placebos) in the morning of Day 15 under fasted conditions. The first cohort will receive a 0.1 mg dose. Cohorts will continue to be enrolled at the next higher dose level until the highest dose level (3 mg) has been achieved or until the study is discontinued due to adverse events or Clinical Opioid Withdrawal Score of >8. A 0.03 mg dose will also be tested. A 0.01 mg dose will be tested if 4 or more subjects experience 1 or more bowel movements within the 24 hour period post dose in the 0.03 mg dosing cohort.
- Conditions
- Opioid Induced Bowel Dysfunction
- Being tested
- Naldemedine, Placebo
- Keywords
- Chronic pain, Opioid physical dependence
- Medical subject headings
- Opioid-Induced Constipation, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaldemedineDrug
Also called S-297995, Symproic®
Tablets or solution for oral administration
PlaceboDrug
Tablets or solution for oral administration
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | In this cohort 9 participants received one 0.1 mg naldemedine tablet and 3 participants received matching placebo administered on Day 15 under fasted conditions. Receives: Drug: Naldemedine; Drug: Placebo |
| Cohort 2 | Experimental | In this cohort 9 participants received a single dose of 0.3 mg naldemedine tablets and 3 participants received matching placebo tablets administered on Day 15 under fasted conditions. Receives: Drug: Naldemedine; Drug: Placebo |
| Cohort 3 | Experimental | In this cohort 9 participants received a single dose of 1 mg naldemedine tablets and 3 participants received matching placebo tablets administered on Day 15 under fasted conditions. Receives: Drug: Naldemedine; Drug: Placebo |
| Cohort 4 | Experimental | In this cohort 9 participants received a single dose of 3 mg naldemedine tablets and 3 participants received matching placebo tablets administered on Day 15 under fasted conditions. Receives: Drug: Naldemedine; Drug: Placebo |
| Cohort 5 | Experimental | In this cohort 9 participants received a single dose of 0.03 mg naldemedine oral solution and 3 participants received matching placebo oral solution administered on Day 15 under fasted conditions. Receives: Drug: Naldemedine; Drug: Placebo |
| Cohort 6 | Experimental | In this cohort 9 participants received a single dose of 0.01 mg naldemedine oral solution and 3 participants received matching placebo oral solution administered on Day 15 under fasted conditions. Receives: Drug: Naldemedine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
Severity of adverse events (AEs) was graded according to the following definitions:
- Mild: The subject experiences awareness of symptoms but these are easily tolerated or managed without specific treatment
- Moderate: The subject experiences discomfort enough to cause interference with usual activity, and/or the condition requires specific treatment
- Severe: The subject is incapacitated with inability to work or do usual activity, and/or the event requires significant treatment measures.
The relationship of the event to the study drug was determined by the investigator.
A serious adverse event (SAE) is defined as any AE occurring at any dose that resulted in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Measured: From the first dose of study drug on Day 15 up to Day 24.
Secondary outcomes (25)
Change From Baseline to 24 Hours Post-dose in Number of Spontaneous Bowel Movements (SBMs) Per Day
Participants completed a bowel function assessment daily diary to record information about bowel movements and constipation. A spontaneous bowel movement was defined as a bowel movement where no laxative or enema was used in the 24 hours preceding the bowel movement.
Baseline was defined as the average number of SBMs per day during the 2 weeks prior to receiving study drug (Day 1 to Day 15).
Measured: Baseline (Day 1 to Day 15) and Day 15 to 16 (0 to 24 hours post-dose)
Change From Baseline to 48 Hours Post-dose in the Number of SBMs Per Day
Participants completed a bowel function assessment daily diary to record information about bowel movements and constipation. A spontaneous bowel movement was defined as a bowel movement where no laxative or enema was used in the 24 hours preceding the bowel movement. Baseline was defined as the average number of SBMs per day during the 2 weeks prior to receiving study drug (Day 1 to Day 15). Forty-eight hours post-dose was defined as the average number of SBMs per day from 0 to 48 hours post-dose.
Measured: Baseline (Day 1 to Day 15) and Day 15 to Day 17 (0 to 48 hours post-dose)
Change From Baseline to 24 Hours Post-dose in Number of Bowel Movements (BM) Per Day
Participants completed a bowel function assessment daily diary to record information about bowel movements and constipation. Baseline was defined as the average number of BMs per day during the 2 weeks prior to receiving study drug (Day 1 to Day 15).
Measured: Baseline and 24 hours post-dose
Change From Baseline to 48 Hours Post-dose in Number of Bowel Movements Per Day
Participants completed a bowel function assessment daily diary to record information about bowel movements and constipation. Baseline was defined as the average number of BMs per day during the 2 weeks prior to receiving study drug (Day 1 to Day 15). Forty-eight hours post-dose was defined as the average number of BMs per day from 0 to 48 hours post-dose.
Measured: Baseline and 48 hours post-dose
Change From Baseline to 24 Hours Post-dose in Number of Complete Spontaneous Bowel Movements (CSBMs) Per Day
Participants completed a bowel function assessment daily diary to record information about bowel movements and constipation. A complete spontaneous bowel movement was defined as a bowel movement where no laxative or enema was used and the bowel movement resulted in a sensation of complete evacuation (based on the question of "having a feeling of complete emptying after the bowel movement").
Baseline was defined as the average number of CSBMs per day during the 2 weeks prior to receiving study drug (Day 1 to Day 15).
Measured: Baseline and 24 hours post-dose
Change From Baseline to 48 Hours Post-dose in Number of Complete Spontaneous Bowel Movements (CSBMs) Per Day
Participants completed a bowel function assessment daily diary to record information about bowel movements and constipation. A complete spontaneous bowel movement was defined as a bowel movement where no laxative or enema was used and the bowel movement resulted in a sensation of complete evacuation (based on the question of "having a feeling of complete emptying after the bowel movement").
Baseline was defined as the average number of CSBMs per day during the 2 weeks prior to receiving study drug (Day 1 to Day 15). Forty-eight hours post-dose was defined as the average number of CSBMs per day from 0 to 48 hours post-dose.
Measured: Baseline and 48 hours post-dose
Time to First Spontaneous Bowel Movement
The time to first SBM during the Study Drug Administration Period was summarized using Kaplan-Meier estimates. Each participant's first SBM was counted as an event and the time to first SBM after dosing was calculated from the date and time of first dosing until the date and time of first SBM. Participants who dropped out or were lost to follow-up before the first SBM were censored.
Measured: From first dose on Day 15 through Day 17
Time to First Bowel Movement
The time to first BM during the Study Drug Administration Period was summarized using Kaplan-Meier estimates. Each participant's first BM was counted as an event and the time to first BM after dosing was calculated from the date and time of first dosing until the date and time of first BM. Participants who dropped out or were lost to follow-up before the first BM were censored.
Measured: From first dose on Day 15 through Day 17
Time to First Complete Spontaneous Bowel Movement
The time to first CSBM during the Study Drug Administration Period was summarized using Kaplan-Meier estimates. Each participant's first CSBM was counted as an event and the time to first CSBM after dosing was calculated from the date and time of first dosing until the date and time of first CSBM. Participants who dropped out or were lost to follow-up before the first CSBM were censored.
Measured: From first dose on Day 15 through Day 17
Change From Baseline in Straining During Bowel Movements
Straining during BMs was graded using the following scale: 0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe.
Baseline was defined as the average straining score of all BMs prior to receiving study drug (Day 1 to Day 15). The straining score at 24 and 48 hours post-dose was calculated as the average straining score from all bowel movements from 0 to 24 and 0 to 48 hours post-dose, respectively.
Measured: Baseline, 24 hours post-dose and 48 hours post-dose
Change From Baseline to 24 Hours Post-dose in Number of Complete Bowel Movements Per Day
A complete bowel movement (CBM) was defined as a bowel movement that resulted in a sensation of complete evacuation based on the question "Did you have a feeling of complete emptying after the bowel movement?" Baseline was defined as the average number of CBMs per day prior to receiving study drug (Day 1 to Day 15).
Measured: Baseline and 24 hours post-dose
Change From Baseline to 48 Hours Post-dose in Number of Complete Bowel Movements Per Day
A complete bowel movement (CBM) was defined as a bowel movement that resulted in a sensation of complete evacuation based on the question "Did you have a feeling of complete emptying after the bowel movement?" Baseline was defined as the average number of CBMs per day prior to receiving study drug (Day 1 to 15). Forty-eight hours post-dose was calculated as the average number of CBMs per day from 0 to 48 hours post-dose.
Measured: Baseline and 48 hours post-dose
Change From Baseline in Abdominal Bloating
Participants were asked to rate their abdominal bloating for the past 24 hours using the following scale:
0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe. Baseline was defined as the average abdominal bloating score prior to receiving study drug (Day 1 to Day 15). Abdominal bloating at 24 hours and 48 hours post-dose was calculated as the mean score from 0 to 24 and 0 to 48 hours post-dose respectively.
Measured: Baseline, 24 hours post-dose and 48 hours post-dose
Change From Baseline in Abdominal Discomfort
Participants were asked to rate their abdominal discomfort for the past 24 hours using the following scale:
0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe. Baseline was defined as the average abdominal discomfort score prior to receiving study drug (Day 1 to Day 15). Abdominal discomfort at 24 hours and 48 hours post-dose was calculated as the mean score from 0 to 24 and 0 to 48 hours post-dose respectively.
Measured: Baseline, 24 hours post-dose and 48 hours post-dose
Change From Baseline in BM Consistency
Consistency of BMs was measured using the Bristol Stool Scale, as follows:
1 = separate hard lumps like nuts; 2 = sausage shaped but lumpy; 3 = like a sausage, but with cracks on its surface; 4 = like a sausage or a snake, smooth and soft; 5 = soft blobs and with clear-cut edges; 6 = floppy pieces with ragged edges/mushy stool; 7 = watery, no solid pieces, entirely liquid.
Baseline was defined as the average consistency of BMs prior to receiving study drug (Day 1 to Day 15). BM consistency at 24 hours and 48 hours post-dose was calculated as the average scores from all bowel movements from 0 to 24 and 0 to 48 hours post-dose, respectively.
Measured: Baseline, 24 hours post-dose and 48 hours post-dose
Change From Baseline in Number of False Start Bowel Movements Per Day
A false start was defined as any attempted, but unsuccessful bowel movement (no solid or liquid fecal material was excreted) based on the question "In the past 24 hours, how many times did you try to have a bowel movement but were unsuccessful?" Baseline was defined as the average number of false start BMs per day prior to receiving study drug (Day 1 to Day 15).
The number of false start BMs per day at 24 hours and 48 hours post-dose was calculated as is the average number of false start BMs per day from 0 to 24 and 0 to 48 hours post-dose, respectively.
Measured: Baseline, 24 hours post-dose and 48 hours post-dose
Change From Baseline in the Number of Bowel Movements With No Straining Per Day
Straining during BMs was graded using the following scale:
0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe. A BM without straining was defined as a BM with a straining score = 0.
Baseline was defined as the average number of BMs without straining per day prior to receiving study drug (Day 1 to Day 15). The number of BMs without straining per day at 24 hours and 48 hours post-dose was calculated as the average number of BMs with no straining per day from 0 to 24 hours and 0 to 48 hours post-dose, respectively.
Measured: Baseline, 24 hours post-dose and 48 hours post-dose
Change From Baseline in Number of Rescue Medications Used Per Day
Baseline was defined as the average number of rescue medications used per day prior to receiving study drug (Day 1 to Day 15). The number of rescue medications used per day at 24 hours and 48 hours post-dose was calculated as the average number of rescue medications used per day from 0 to 24 hours and 0 to 48 hours post-dose, respectively.
Measured: Baseline, 24 hours post-dose and 48 hours post-dose
Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score > 8 at Any Time During the Study
The COWS assessment consisted of 11 questions which rated the severity of opiate withdrawal symptoms, including resting pulse rate, gastrointestinal upset, sweating, restlessness, pupil size, tremor, anxiety or irritability, bone or joint aches, gooseflesh skin, yawning, and runny nose or tearing. Each symptom was rated on a scale from 0 (not present) to 4 or 5 (most severe). The total score was calculated by summing the 11 individual scores and ranged from 0 (no withdrawal symptoms) to 48 (worst symptoms).
Measured: The COWS assessments were performed at Screening, on Day 14, Day 15 (pre-dose and 1, 2, 3, 4, 5, 6 and 8 hours post-dose, and at unscheduled times as signs or symptoms indicate), on Days 16 and 17, and on Day 24/End of Study.
Percentage of Participants With Webster Opiate Withdrawal Scale (WOWS) Score > 8 at Any Time During the Study
The Webster Opiate Withdrawal Scale (WOWS) assessment consisted of 7 questions which rate the severity of opiate withdrawal symptoms, including sweating, sleep, bone or joint aches, runny nose or tearing, gastrointestinal upset, anxiety or irritability and gooseflesh skin. Each symptom was rated on a scale from 0 (not present/no issues) to 4 or 5 (severe). The total score was calculated by summing the 7 individual scores and ranged from 0 (no withdrawal symptoms) to 29 (worst symptoms).
Measured: The WOWS assessment was performed at Screening, Day 14, Day 15 at pre-dose , and 24 and 48 hours post-dose and at the Follow-up/End of Study visit (Day 24).
Maximum Observed Plasma Concentration (Cmax) of Naldemedine and Metabolite Nor-S-297995
The plasma concentration of naldemedine and its metabolite Nor-S-297995 were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) method.
Measured: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Time to Maximum Observed Plasma Concentration of Naldemedine and Metabolite Nor-S-297995
The plasma concentration of naldemedine and its metabolite Nor-S-297995 were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) method.
Measured: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration of Naldemedine and Metabolite Nor-S-297995
The plasma concentration of naldemedine and its metabolite Nor-S-297995 were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. Area under the plasma concentration versus time curve from time zero to the last sampling time at which concentrations were at or above the limit of quantitation, calculated using the linear trapezoidal rule for increasing concentrations and the logarithmic rule for decreasing concentrations (Linear Up/ Log Down).
Measured: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity for Naldemedine and Metabolite Nor-S-297995
The plasma concentration of naldemedine and its metabolite Nor-S-297995 were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. Area under the plasma concentration versus time curve from time zero to infinity, calculated using the formula: AUC0-inf = AUC0-t + Ct/λZ where Ct was the last measurable concentration and λZ was the apparent terminal elimination rate constant.
Measured: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Apparent Elimination Half-life of Naldemedine and Metabolite Nor-S-297995
The plasma concentration of naldemedine and its metabolite Nor-S-297995 were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. The apparent elimination half-life was calculated using the formula t1/2,z = (ln2)/λZ
Measured: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2010 (estimated)
- Study start19 May 2010
- Primary completion23 Feb 2011
- Study completion22 Mar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Opioid Induced Bowel DysfunctionStudies of the same condition, open and under way.
- More trials run by ShionogiThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shionogi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shionogi Clinical Trials Administrator Clinical Support Help Line, Study director, Shionogi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01122030
- Sponsor's protocol ID
- 1007V9214
- Status last verified
- Sep 2011
- First submitted
- 10 May 2010
- Last updated
- 30 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety and Efficacy of S-297995 for the Treatment of Opioid-Induced Bowel Dysfunction in Subjects With Chronic Pain
- ClinicalTrials.gov ID
- NCT01122030
- Acronym / sponsor ID
- 1007V9214
- Conditions
- Opioid Induced Bowel Dysfunction
- Keywords
- Chronic pain, Opioid physical dependence
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- ShionogiIndustry (pharma, biotech, devices)
- Study start
- 19 May 2010 (actual)
- Primary completion
- 23 Feb 2011 (actual)
- Study completion
- 22 Mar 2011 (actual)
- First posted
- 12 May 2010 (estimated)
- Results
- Posted 30 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the study is to evaluate the safety of single doses of oral naldemedine in adults physically dependent on opioids.
Detailed description
A single dose of naldemedine or matching placebo will be administered orally to each cohort of 12 participants (9 treatments, 3 placebos) in the morning of Day 15 under fasted conditions. The first cohort will receive a 0.1 mg dose. Cohorts will continue to be enrolled at the next higher dose level until the highest dose level (3 mg) has been achieved or until the study is discontinued due to adverse events or Clinical Opioid Withdrawal Score of >8. A 0.03 mg dose will also be tested. A 0.01 mg dose will be tested if 4 or more subjects experience 1 or more bowel movements within the 24 hour period post dose in the 0.03 mg dosing cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Naldemedine, Drug: PlaceboIn this cohort 9 participants received one 0.1 mg naldemedine tablet and 3 participants received matching placebo administered on Day 15 under fasted conditions. |
| Cohort 2 | Experimental | Drug: Naldemedine, Drug: PlaceboIn this cohort 9 participants received a single dose of 0.3 mg naldemedine tablets and 3 participants received matching placebo tablets administered on Day 15 under fasted conditions. |
| Cohort 3 | Experimental | Drug: Naldemedine, Drug: PlaceboIn this cohort 9 participants received a single dose of 1 mg naldemedine tablets and 3 participants received matching placebo tablets administered on Day 15 under fasted conditions. |
| Cohort 4 | Experimental | Drug: Naldemedine, Drug: PlaceboIn this cohort 9 participants received a single dose of 3 mg naldemedine tablets and 3 participants received matching placebo tablets administered on Day 15 under fasted conditions. |
| Cohort 5 | Experimental | Drug: Naldemedine, Drug: PlaceboIn this cohort 9 participants received a single dose of 0.03 mg naldemedine oral solution and 3 participants received matching placebo oral solution administered on Day 15 under fasted conditions. |
| Cohort 6 | Experimental | Drug: Naldemedine, Drug: PlaceboIn this cohort 9 participants received a single dose of 0.01 mg naldemedine oral solution and 3 participants received matching placebo oral solution administered on Day 15 under fasted conditions. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Understand and sign an informed consent form
- Males will agree to use an approved double-barrier method of contraception from Day 1 until 1 month after study completion
- Subject tests negative on urine drug test unless the subject has a prescription for the drug(s) that test positive
Key exclusion criteria (4 listed)
- Subjects under opioid therapy for cancer-related pain or for the management of drug addiction
- Fecal incontinence, irritable bowel syndrome, inflammatory bowel disease, or other active medical disorders associated with diarrhea, intermittent loose stools, or constipation
- Subjects who have participated in any other investigational drug study within 30 days prior to Day 1
- Prior exposure to S-297995
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 |
|---|---|---|
| NaldemedineAlso: S-297995, Symproic®Tablets or solution for oral administration | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6 |
| PlaceboTablets or solution for oral administration | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6 |
Primary outcome
Number of Participants With Adverse Events
Time frame: From the first dose of study drug on Day 15 up to Day 24.
Severity of adverse events (AEs) was graded according to the following definitions: * Mild: The subject experiences awareness of symptoms but these are easily tolerated or managed without specific treatment * Moderate: The subject experiences discomfort enough to cause interference with usual activity, and/or the condition requires specific treatment * Severe: The subject is incapacitated with inability to work or do usual activity, and/or the event requires significant treatment measures. The relationship of the event to the study drug was determined by the investigator. A serious adverse event (SAE) is defined as any AE occurring at any dose that resulted in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
25 secondary outcomes
Change From Baseline to 24 Hours Post-dose in Number of Spontaneous Bowel Movements (SBMs) Per Day
Time frame: Baseline (Day 1 to Day 15) and Day 15 to 16 (0 to 24 hours post-dose)
Change From Baseline to 48 Hours Post-dose in the Number of SBMs Per Day
Time frame: Baseline (Day 1 to Day 15) and Day 15 to Day 17 (0 to 48 hours post-dose)
Change From Baseline to 24 Hours Post-dose in Number of Bowel Movements (BM) Per Day
Time frame: Baseline and 24 hours post-dose
Change From Baseline to 48 Hours Post-dose in Number of Bowel Movements Per Day
Time frame: Baseline and 48 hours post-dose
Change From Baseline to 24 Hours Post-dose in Number of Complete Spontaneous Bowel Movements (CSBMs) Per Day
Time frame: Baseline and 24 hours post-dose
Change From Baseline to 48 Hours Post-dose in Number of Complete Spontaneous Bowel Movements (CSBMs) Per Day
Time frame: Baseline and 48 hours post-dose
Time to First Spontaneous Bowel Movement
Time frame: From first dose on Day 15 through Day 17
Time to First Bowel Movement
Time frame: From first dose on Day 15 through Day 17
Time to First Complete Spontaneous Bowel Movement
Time frame: From first dose on Day 15 through Day 17
Change From Baseline in Straining During Bowel Movements
Time frame: Baseline, 24 hours post-dose and 48 hours post-dose
Change From Baseline to 24 Hours Post-dose in Number of Complete Bowel Movements Per Day
Time frame: Baseline and 24 hours post-dose
Change From Baseline to 48 Hours Post-dose in Number of Complete Bowel Movements Per Day
Time frame: Baseline and 48 hours post-dose
Change From Baseline in Abdominal Bloating
Time frame: Baseline, 24 hours post-dose and 48 hours post-dose
Change From Baseline in Abdominal Discomfort
Time frame: Baseline, 24 hours post-dose and 48 hours post-dose
Change From Baseline in BM Consistency
Time frame: Baseline, 24 hours post-dose and 48 hours post-dose
Change From Baseline in Number of False Start Bowel Movements Per Day
Time frame: Baseline, 24 hours post-dose and 48 hours post-dose
Change From Baseline in the Number of Bowel Movements With No Straining Per Day
Time frame: Baseline, 24 hours post-dose and 48 hours post-dose
Change From Baseline in Number of Rescue Medications Used Per Day
Time frame: Baseline, 24 hours post-dose and 48 hours post-dose
Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score > 8 at Any Time During the Study
Time frame: The COWS assessments were performed at Screening, on Day 14, Day 15 (pre-dose and 1, 2, 3, 4, 5, 6 and 8 hours post-dose, and at unscheduled times as signs or symptoms indicate), on Days 16 and 17, and on Day 24/End of Study.
Percentage of Participants With Webster Opiate Withdrawal Scale (WOWS) Score > 8 at Any Time During the Study
Time frame: The WOWS assessment was performed at Screening, Day 14, Day 15 at pre-dose , and 24 and 48 hours post-dose and at the Follow-up/End of Study visit (Day 24).
Maximum Observed Plasma Concentration (Cmax) of Naldemedine and Metabolite Nor-S-297995
Time frame: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Time to Maximum Observed Plasma Concentration of Naldemedine and Metabolite Nor-S-297995
Time frame: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration of Naldemedine and Metabolite Nor-S-297995
Time frame: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity for Naldemedine and Metabolite Nor-S-297995
Time frame: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Apparent Elimination Half-life of Naldemedine and Metabolite Nor-S-297995
Time frame: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Results and safety
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Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Recruiting
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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.
Shionogi Clinical Trials Administrator Clinical Support Help Line study director
Shionogi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Naldemedine in people with Opioid Induced Bowel Dysfunction, run by Shionogi at 1 site in United States.
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 3 inclusion and 4 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 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Adverse Events (time frame: From the first dose of study drug on Day 15 up to Day 24.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 May 2017; AzTrials last refreshed its copy on 8 Nov 2026.