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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-002948-91 | EudraCT Number |
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The purpose of this study is to evaluate the efficacy and safety of naldemedine in the treatment of opioid-induced constipation (OIC) in adults with non-malignant chronic pain who are not using laxatives.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Naldemedine | Experimental | Participants received 0.2 mg naldemedine orally once daily for 12 weeks. |
|
| Placebo | Placebo Comparator | Participants received matching placebo orally once daily for 12 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Naldemedine | Drug | Naldemedine 0.2 mg tablet taken orally once a day |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With a Spontaneous Bowel Movement (SBM) Response | A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. An SBM was defined as a bowel movement that occurred without the use of rescue laxative therapy during the 24 hours prior to the BM. A responder was defined as a participant having 9 or more positive response weeks out of the 12-week Treatment Period and 3 positive response weeks out of last 4 weeks of the 12-week Treatment Period. A positive response week was defined as ≥ 3 SBMs per week and an increase from baseline of ≥ 1 SBM per week for that week. If a participant had less than 4 days of diary entries for a week, that week was treated as a "non-response" week. Any participant with insufficient primary endpoint data (data for less than 9 out of the 12 weeks of the Treatment Period or less than 3 out of the last 4 weeks of the 12-week Treatment Period) was treated as a non-responder | 12-week treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week | A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. An SBM was defined as a bowel movement that occurred without the use of a rescue laxative therapy during the 24 hours prior to the BM. Baseline was defined as the 14 days in the screening period prior to study drug administration. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shionogi Clinical Trials Administrator Clinical Support Help Line | Shionogi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shionogi Research Site | Birmingham | Alabama | United States | |||
| Shionogi Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34377150 | Derived | Hale ME, Wild JE, Yamada T, Yokota T, Tack J, Andresen V, Drewes AM. Naldemedine is effective in the treatment of opioid-induced constipation in patients with chronic non-cancer pain who had a poor response to laxatives. Ther Adv Gastroenterol. 2021 Jul 31;14:17562848211032320. doi: 10.1177/17562848211032320. eCollection 2021. | |
| 34295186 |
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Participants were randomized in a 1:1 ratio to 0.2 mg naldemedine or placebo for 12 weeks. Randomization was stratified based on documented opioid use (average total daily dose (TDD) during the 14-consecutive-day qualifying period) as follows:
Participants were randomized at 69 sites in North America and Europe, including Austria, Czech Republic, Germany, Poland, Spain, and the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | Naldemedine | Participants received 0.2 mg naldemedine orally once daily for 12 weeks. |
| FG001 | Placebo | Participants received placebo orally once daily for 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Placebo | Drug | Placebo tablet taken orally once a day |
|
| Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment) |
| Change From Baseline to Week 1 in the Number of Spontaneous Bowel Movements Per Week | A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. An SBM was defined as a bowel movement that occurred without the use of a rescue laxative therapy during the 24 hours prior to the BM. Baseline was defined as the 14 days in the screening period prior to study drug administration. | Baseline and Week 1 |
| Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Spontaneous Bowel Movements Per Week | A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. A complete spontaneous bowel movement (CSBM) was defined as an SBM which was accompanied by the feeling of complete evacuation. | Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment) |
| Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements With No Straining Per Week | A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. The severity of straining with each bowel movement was assessed on the following scale: 0=no straining, 1=mild straining, 2=moderate straining, 3=severe straining, 4=very severe straining. SBMs without straining were defined as SBMs with a straining score of 0. | Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment) |
| Homewood |
| Alabama |
| United States |
| Shionogi Research Site | Goodyear | Arizona | United States |
| Shionogi Research Site | Little Rock | Arkansas | United States |
| Shionogi Research Site | Anaheim | California | United States |
| Shionogi Research Site | Buena Park | California | United States |
| Shionogi Research Site | Corona | California | United States |
| Shionogi Research Site | Gold River | California | United States |
| Shionogi Research Site | Los Angeles | California | United States |
| Shionogi Research Site | Modesto | California | United States |
| Shionogi Research Site | Pasadena | California | United States |
| Shionogi Research Site | Coral Gables | Florida | United States |
| Shionogi Research Site | Hialeah | Florida | United States |
| Shionogi Research Site | Jacksonville | Florida | United States |
| Shionogi Research Site | Miami | Florida | United States |
| Shionogi Research Site | Miami Beach | Florida | United States |
| Shionogi Research Site | Plantation | Florida | United States |
| Shionogi Research Site | Columbus | Georgia | United States |
| Shionogi Research Site | Evansville | Indiana | United States |
| Shionogi Research Site | Indianapolis | Indiana | United States |
| Shionogi Research Site | West Des Moines | Iowa | United States |
| Shionogi Research Site | Edgewood | Kentucky | United States |
| Shionogi Research Site | Crowley | Louisiana | United States |
| Shionogi Research Site | Kalamazoo | Michigan | United States |
| Shionogi Research Site | Traverse City | Michigan | United States |
| Shionogi Research Site | Butte | Montana | United States |
| Shionogi Research Site | Omaha | Nebraska | United States |
| Shionogi Research Site | Las Vegas | Nevada | United States |
| Shionogi Research Site | Omaha | Nevada | United States |
| Shionogi Research Site | Albuquerque | New Mexico | United States |
| Shionogi Research Site | Hopewell Junction | New York | United States |
| Shionogi Research Site | Mooresville | North Carolina | United States |
| Shionogi Research Site | Winston-Salem | North Carolina | United States |
| Shionogi Research Site | Dayton | Ohio | United States |
| Shionogi Research Site | Marion | Ohio | United States |
| Shionogi Research Site | Media | Pennsylvania | United States |
| Shionogi Research Site | Spartanburg | South Carolina | United States |
| Shionogi Research Site | Knoxville | Tennessee | United States |
| Shionogi Research Site | Tullahoma | Tennessee | United States |
| Shionogi Research Site | Channelview | Texas | United States |
| Shionogi Research Site | Fort Worth | Texas | United States |
| Shionogi Research Site | Groesbeck | Texas | United States |
| Shionogi Research Site | Houston | Texas | United States |
| Shionogi Research Site | Plano | Texas | United States |
| Shionogi Research Site | San Antonio | Texas | United States |
| Shionogi Research Site | Chesapeake | Virginia | United States |
| Shionogi Research Site | Chester | Virginia | United States |
| Shionogi Research Site | Tacoma | Washington | United States |
| Shionogi Research Site | Clarksburg | West Virginia | United States |
| Camilleri M, Hale M, Morlion B, Tack J, Webster L, Wild J. Naldemedine Improves Patient-Reported Outcomes of Opioid-Induced Constipation in Patients with Chronic Non-Cancer Pain in the COMPOSE Phase 3 Studies. J Pain Res. 2021 Jul 16;14:2179-2189. doi: 10.2147/JPR.S282738. eCollection 2021. |
| 33965574 | Derived | Tack J, Camilleri M, Hale M, Morlion B, Nalamachu S, Webster L, Wild J. Establishing Minimal Clinically Important Differences in Quality of Life Measures in Opioid-Induced Constipation. Clin Gastroenterol Hepatol. 2022 Apr;20(4):855-863. doi: 10.1016/j.cgh.2021.05.004. Epub 2021 Aug 5. |
| 32280263 | Derived | Webster LR, Hale ME, Yamada T, Wild JE. A Renal Impairment Subgroup Analysis of the Safety and Efficacy of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Non-Cancer Pain Receiving Opioid Therapy. J Pain Res. 2020 Mar 24;13:605-612. doi: 10.2147/JPR.S237833. eCollection 2020. |
| 32086791 | Derived | Wild J, Webster L, Yamada T, Hale M. Safety and Efficacy of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Non-Cancer Pain Receiving Opioid Therapy: A Subgroup Analysis of Patients >/= 65 Years of Age. Drugs Aging. 2020 Apr;37(4):271-279. doi: 10.1007/s40266-020-00753-2. |
| 31145214 | Derived | Wild J, Yamada T, Arjona Ferreira JC, Hale M. Onset of action of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: results from 2 randomized, placebo-controlled, phase 3 trials. Pain. 2019 Oct;160(10):2358-2364. doi: 10.1097/j.pain.0000000000001629. |
| 28576452 | Derived | Hale M, Wild J, Reddy J, Yamada T, Arjona Ferreira JC. Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials. Lancet Gastroenterol Hepatol. 2017 Aug;2(8):555-564. doi: 10.1016/S2468-1253(17)30105-X. Epub 2017 May 30. |
| Received Treatment |
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| COMPLETED |
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| NOT COMPLETED |
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The Intent-to-treat (ITT) population included all randomized participants. Three participants (one in the naldemedine arm and two in the placebo arm) were excluded due to double enrollment at different sites.
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| ID | Title | Description |
|---|---|---|
| BG000 | Naldemedine | Participants received 0.2 mg naldemedine orally once daily for 12 weeks. |
| BG001 | Placebo | Participants received placebo orally once daily for 12 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Age, Customized | Number | participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Stratification by Opioid Dose | Dose of opioid was calculated using maintenance and breakthrough morphine equivalent dose. If any participants were treated with < 30 mg, the participants were counted in the '30-100 mg' group. | Number | participants |
| |||||||||||||||
| Spontaneous Bowel Movements per Week | A spontaneous bowel movement was defined as a bowel movement that occurred without the use of a rescue laxative therapy during the 24 hours prior to the bowel movement. | Mean | Standard Deviation | spontaneous bowel movements / week |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With a Spontaneous Bowel Movement (SBM) Response | A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. An SBM was defined as a bowel movement that occurred without the use of rescue laxative therapy during the 24 hours prior to the BM. A responder was defined as a participant having 9 or more positive response weeks out of the 12-week Treatment Period and 3 positive response weeks out of last 4 weeks of the 12-week Treatment Period. A positive response week was defined as ≥ 3 SBMs per week and an increase from baseline of ≥ 1 SBM per week for that week. If a participant had less than 4 days of diary entries for a week, that week was treated as a "non-response" week. Any participant with insufficient primary endpoint data (data for less than 9 out of the 12 weeks of the Treatment Period or less than 3 out of the last 4 weeks of the 12-week Treatment Period) was treated as a non-responder | Intent-to-treat population | Posted | Number | 95% Confidence Interval | percentage of participants | 12-week treatment period |
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| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week | A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. An SBM was defined as a bowel movement that occurred without the use of a rescue laxative therapy during the 24 hours prior to the BM. Baseline was defined as the 14 days in the screening period prior to study drug administration. | Intent-to-treat population | Posted | Least Squares Mean | Standard Error | spontaneous bowel movements / week | Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment) |
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| Secondary | Change From Baseline to Week 1 in the Number of Spontaneous Bowel Movements Per Week | A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. An SBM was defined as a bowel movement that occurred without the use of a rescue laxative therapy during the 24 hours prior to the BM. Baseline was defined as the 14 days in the screening period prior to study drug administration. | Intent-to-treat population | Posted | Least Squares Mean | Standard Error | spontaneous bowel movements / week | Baseline and Week 1 |
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| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Spontaneous Bowel Movements Per Week | A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. A complete spontaneous bowel movement (CSBM) was defined as an SBM which was accompanied by the feeling of complete evacuation. | Intent-to-treat population | Posted | Least Squares Mean | Standard Error | complete spontaneous BMs / week | Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment) |
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| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements With No Straining Per Week | A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. The severity of straining with each bowel movement was assessed on the following scale: 0=no straining, 1=mild straining, 2=moderate straining, 3=severe straining, 4=very severe straining. SBMs without straining were defined as SBMs with a straining score of 0. | Intent-to-treat population | Posted | Least Squares Mean | Standard Error | SBMs with no straining / week | Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment) |
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From the first dose up to 28 days after the last dose of study drug (16 weeks).
The Safety Population included all randomized participants who received at least 1 dose of study drug and were analyzed by the treatment actually received. Three participants (one in the naldemedine arm and two in the placebo arm) were excluded due to double enrollment at different sites.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Naldemedine | Participants received 0.2 mg naldemedine orally once daily for 12 weeks. | 9 | 271 | 37 | 271 | ||
| EG001 | Placebo | Participants received placebo orally once daily for 12 weeks. | 13 | 274 | 20 | 274 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastroenteritis Viral | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Herpes Zoster | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
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| Pneumonia Influenzal | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
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| Bladder Transitional Cell Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
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| Lymphadenopathy Mediastinal | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
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| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
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| Mental Status Changes | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
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| Psychotic Disorder | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
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| Convulsion | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| Sciatica | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| Cardiac Failure Congestive | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
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| Sick Sinus Syndrome | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
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| Chronic Obstructive Pulmonary Disease | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Colitis Ischaemic | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Duodenitis | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Enterocolitis | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
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| Musculoskeletal Chest Pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
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| Renal Failure Acute | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
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| Overdose | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
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| Radius Fracture | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
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| Tendon Rupture | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urinary Tract Infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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The sponsor can embargo results from a PI's center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 60 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Shionogi Clinical Trials Administrator | Shionogi Inc. | 800-849-9707 | 1454 | shionogiclintrials-admin@shionogi.co.jp |
| ID | Term |
|---|---|
| D000079689 | Opioid-Induced Constipation |
| ID | Term |
|---|---|
| D003248 | Constipation |
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C000620491 | naldemedine |
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| ≥ 40 to < 65 years |
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| ≥ 65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Black or African American |
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| Native Hawaiian or Other Pacific Islander |
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| White |
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| > 100 mg |
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