| Primary | Change From Baseline to Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A spontaneous bowel movement was defined as a bowel movement unassisted by rescue medication (laxative or enema) taken within the 24 hours preceding the bowel movement. Baseline was defined as the average number of SBMs per week during the 2 weeks prior to randomization. The number of SBMs per week in the last 2 weeks of treatment is defined as the average number of SBMs per week recorded in the diary for the 14 days prior to the last dose of study drug. | Modified intention-to-treat population | Posted | | Least Squares Mean | Standard Error | spontaneous bowel movements per week | | Baseline (2 weeks prior to randomization) and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
| | Units | Counts |
|---|
| Participants | - OG00061
- OG00161
- OG00259
- OG003
|
| | Title | Denominators | Categories |
|---|
| | | Title | Measurements |
|---|
| - OG0001.42± 0.422
- OG0011.98± 0.422
- OG0023.37± 0.429
- OG003
|
|
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| | ANCOVA | Analysis of covariance (ANCOVA) model with treatment group as a term and baseline value as a covariate. | 0.0003 | | LS Mean Difference | 2.22 | Standard Error of the Mean | 0.605 | 2-Sided | 95 | 1.02 | 3.41 | | | | | Superiority or Other | | | | | ANCOVA |
|
| Secondary | Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Spontaneous Bowel Movements Per Week | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A spontaneous bowel movement was defined as a bowel movement unassisted by rescue medication (laxative or enema) taken within the 24 hours preceding the bowel movement. Baseline was defined as the average number of SBMs per day during the 2 weeks prior to randomization. | mITT population with values at both baseline and the specified time point. | Posted | | Least Squares Mean | Standard Error | spontaneous bowel movements per week | | Baseline and Weeks 1, 2, 3, and 4 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg |
|
| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Bowel Movements (BMs) Per Week | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A BM was defined as all bowel movements observed irrespective of the use of a laxative agent. | | Posted | | Least Squares Mean | Standard Error | bowel movements per week | | Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Bowel Movements Per Week | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A BM was defined as all bowel movements observed irrespective of the use of a laxative agent. | mITT population with values at both baseline and the specified time point. | Posted | | Least Squares Mean | Standard Error | bowel movements per week | | Baseline and Weeks 1, 2, 3, and 4 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Bowel Movements (CBMs) Per Week | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A complete BM (CBM) was defined as a BM where the participant answered 'Yes' to the following question: 'Did you have a feeling of complete emptying after the bowel movement?' | | Posted | | Least Squares Mean | Standard Error | complete bowel movements per week | | Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | |
|
| Secondary | Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Complete Bowel Movements Per Week | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A complete BM (CBM) was defined as a BM where the participant answered 'Yes' to the following question: 'Did you have a feeling of complete emptying after the bowel movement?' | mITT population with values at both baseline and the specified time point. | Posted | | Least Squares Mean | Standard Error | complete bowel movements per week | | Baseline and Weeks 1, 2, 3, and 4 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Spontaneous Bowel Movements (CSBMs) Per Week | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A CSBM was defined as a spontaneous BM which was accompanied by the feeling of complete evacuation. | | Posted | | Least Squares Mean | Standard Error | complete spontaneous BMs per week | | Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Complete Spontaneous Bowel Movements Per Week | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A CSBM was defined as a spontaneous BM which was accompanied by the feeling of complete evacuation. | mITT population with values at both baseline and the specified time point. | Posted | | Least Squares Mean | Standard Error | complete spontaneous BMs per week | | Baseline and Weeks 1, 2, 3, and 4 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Percentage of Participants With an SBM Response in the Last 2 Weeks of the Treatment Period | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. An SBM responder was defined as a participant whose frequency of SBMs within the last 2 weeks of the treatment period was 3 times or more per week and who had an average increase in the frequency of SBMs from baseline of 1 or more per week. | | Posted | | Number | | percentage of participants | | Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | |
|
| Secondary | Percentage of Participants With an SBM Response at Weeks 1, 2, 3 and 4 | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. An SBM responder was defined as any participant whose frequency of SBM per week during the treatment period was 3 times or more per week, and who had an average increase from baseline of 1 or more per week. | mITT population; missing data were imputed using last observation carried forward (LOCF). | Posted | | Number | | percentage of participants | | Baseline and Weeks 1, 2, 3, and 4 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Percentage of Participants With a CSBM Response in the Last 2 Weeks of the Treatment Period | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A CSBM responder was defined as a participant whose frequency of CSBMs within the last 2 weeks of the treatment period was 3 times or more per week and who had an average increase in the frequency of CSBMs from baseline of 1 or more per week. | | Posted | | Number | | percentage of participants | | Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | |
|
| Secondary | Percentage of Participants With a CSBM Response at Weeks 1, 2, 3, and 4 | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A CSBM responder was defined as a participant whose frequency of CSBMs during the treatment period was 3 times or more per week and who had an average increase in the frequency of CSBMs from baseline of 1 or more per week. | mITT population; missing data were imputed using last observation carried forward (LOCF). | Posted | | Number | | percentage of participants | | Baseline and Weeks 1, 2, 3, and 4 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of Days Per Week With SBMs | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. An SBM is defined as a bowel movement unassisted by rescue medication (laxative or enema) taken within the 24 hours preceding the bowel movement. | | Posted | | Least Squares Mean | Standard Error | days/week | | Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Change From Baseline to Weeks 1, 2, 3 and 4 in Number of Days Per Week With SBMs | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. An SBM is defined as a bowel movement unassisted by rescue medication (laxative or enema) taken within the 24 hours preceding the bowel movement. | mITT population with values at both baseline and the specified time point. | Posted | | Least Squares Mean | Standard Error | days/week | | Baseline and Weeks 1, 2, 3, and 4 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of Days Per Week With CSBMs | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A CSBM was defined as a spontaneous BM which was accompanied by the feeling of complete evacuation. | | Posted | | Least Squares Mean | Standard Error | days/week | | Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Change From Baseline to Weeks 1, 2, 3 and 4 in Number of Days Per Week With CSBMs | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A CSBM was defined as a spontaneous BM which was accompanied by the feeling of complete evacuation. | mITT population with values at both baseline and the specified time point. | Posted | | Least Squares Mean | Standard Error | days/week | | Baseline and Weeks 1, 2, 3, and 4 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Time to the First Spontaneous Bowel Movement | Time to the first SBM was defined as the time to the first SBM after the initial administration of study drug. Participants who withdrew from the study before an SBM was observed or had no SBM during the treatment period were treated as censored. | | Posted | | Median | 95% Confidence Interval | hours | | 28 days | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
| |
| Secondary | Time to the First Complete Spontaneous Bowel Movement | Time to the first CSBM was defined as the time to the first CSBM after the initial administration of study drug. Participants who withdrew from the study before a CSBM was observed or had no CSBM during the treatment period were treated as censored. | | Posted | | Median | 95% Confidence Interval | hours | | 28 days | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
| |
| Secondary | Percentage of Participants With SBMs Within 4, 8, 12, and 24 Hours After the Initial Administration of Study Drug | The percentage of participants who experienced at least one SBM within 4, 8, 12, and 24 hours after the initial administration of study drug and before the second administration. | | Posted | | Number | | percentage of participants | | 4, 8, 12, and 24 hours | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
| |
| Secondary | Percentage of Participants With CSBMs Within 4, 8, 12, and 24 Hours After the Initial Administration of Study Drug | The percentage of participants who experienced at least one CSBM within 4, 8, 12, and 24 hours after the initial administration of study drug and before the second administration. | | Posted | | Number | | percentage of participants | | 4, 8, 12, and 24 hours | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
| |
| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of SBMs Per Week Rated as 3 or 4 on the Bristol Stool Scale | Consistency of BMs was measured using the Bristol Stool Scale, according to the following: 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. | | Posted | | Least Squares Mean | Standard Error | spontaneous bowel movements/week | | Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg |
|
| Secondary | Change From Baseline to Weeks 1, 2, 3, and 4 in Number of SBMs Rated as 3 or 4 on the Bristol Stool Scale Per Week | Consistency of BMs was measured using the Bristol Stool Scale, according to the following: 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. | mITT population with values at both baseline and the specified time point. | Posted | | Least Squares Mean | Standard Error | spontaneous bowel movements/week | | Baseline and Weeks 1, 2, 3, and 4 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg |
|
| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of SBMs Per Week With no Straining | Straining during BMs was graded using the following scale: 0 = No straining; 1 = Mild straining; 2 = Moderate; 3 = Severe; 4 = Very Severe. A BM without straining was defined as a BM with a straining score of 0 or 1. | | Posted | | Least Squares Mean | Standard Error | bowel movements/week | | Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of SBMs Per Week Without Straining | Straining during BMs was graded using the following scale: 0 = No straining; 1 = Mild straining; 2 = Moderate; 3 = Severe; 4 = Very Severe. A BM without straining is defined as a BM with a straining score of 0 or 1. | mITT population with values at both baseline and the specified time point. | Posted | | Least Squares Mean | Standard Error | bowel movements/week | | Baseline and Weeks 1, 2, 3, and 4 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of False Start BMs Per Week | Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A false start was defined as any attempted, but unsuccessful bowel movement (no solid or liquid fecal material was excreted). | mITT population with values at both baseline and the last 2 weeks of the treatment period | Posted | | Mean | Standard Deviation | false start BMs | | Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | |
|
| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in Rescue Use of Laxative Agents Per Week | Participants were asked how many doses of rescue laxative medication they had taken within the past 24 hours as part of the Bowel Movement and Constipation Assessment Diary (BMCA). | | Posted | | Mean | Standard Deviation | doses/week | | Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
| |
| Secondary | Mean Rescue Laxative Use Per Week During the Treatment Period | Participants were asked how many doses of rescue laxative medication they had taken within the past 24 hours as part of the Bowel Movement and Constipation Assessment Diary (BMCA). | | Posted | | Mean | Standard Deviation | doses/week | | Weeks 1 to 4 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
| |
| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in Abdominal Bloating | Participants were asked to rate their abdominal bloating for the past 24 hours on a scale of 0 to 4, where 0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe. | mITT population with a value at both baseline and the last 2 weeks of treatment. | Posted | | Mean | Standard Deviation | units on a scale | | Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
|
| Secondary | Change From Baseline to Weeks 1, 2, 3, and 4 in Abdominal Bloating | Participants were asked to rate their abdominal bloating for the past 24 hours on a scale of 0 to 4, where 0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe. | mITT population with a value at both baseline and the specified time point. | Posted | | Mean | Standard Deviation | units on a scale | | Baseline and Weeks 1, 2, 3, and 4 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
| |
| Secondary | Change From Baseline to the Last 2 Weeks of the Treatment Period in Abdominal Discomfort | Participants were asked to rate their abdominal discomfort for the past 24 hours on a scale from 0 to 4, where 0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe. | mITT population with a value at both baseline and the last 2 weeks of treatment. | Posted | | Mean | Standard Deviation | units on a scale | | Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
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| Secondary | Change From Baseline to Weeks 1, 2, 3, and 4 in Abdominal Discomfort | Participants were asked to rate their abdominal discomfort for the past 24 hours on a scale from 0 to 4, where 0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe. | mITT population with a value at both baseline and the specified time point. | Posted | | Mean | Standard Deviation | units on a scale | | Baseline and Weeks 1, 2, 3, and 4 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
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| Secondary | Subject Global Satisfaction at End of Treatment | On day 29 (or at early termination), participants were asked about their degree of satisfaction with constipation and abdominal symptoms from the start of study drug dosing to Day 28 (or early termination visit). The grades were as follows: 1, markedly worsened; 2, moderately worsened; 3, slightly worsened; 4, unchanged; 5, slightly improved; 6, moderately improved; and 7, markedly improved. | | Posted | | Number | | participants | | Day 29, or at early termination | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of Naldemedine and Metabolite Nor-S-297995 | Pharmacokinetic blood samples for naldemedine (S-297995) and its metabolite, Nor-S-297995, were collected from a subset of participants at selected study sites on Day 1 and in a further subset on Day 28. | The PK parameter population (PK population) includes all participants who received study drug with at least one PK parameter estimated adequately on Day 1 or Day 28 | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | Day 1 and Day 28 predose and 1, 2, 4, 8, and 24 hours postdose | | | | ID | Title | Description |
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| OG000 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG001 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
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| Secondary | Time to Maximum Concentration (Tmax) of Naldemedine and Metabolite Nor-S-297995 | Pharmacokinetic blood samples for naldemedine (S-297995) and its metabolite, Nor-S-297995, were collected from a subset of participants at selected study sites on Day 1 and in a further subset on Day 28. | PK population with available data | Posted | | Median | Full Range | hours | | Day 1 and Day 28 predose and 1, 2 , 4, 8, and 24 hours postdose | | | | ID | Title | Description |
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| OG000 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG001 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
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| Secondary | Area Under the Concentration-time Curve From Hour 0 to the Time Point of the Last Measurable Concentration Within the Dose Interval (AUC0-τ) | Pharmacokinetic blood samples for naldemedine (S-297995) and its metabolite, Nor-S-297995, were collected from a subset of participants at selected study sites on Day 1 and in a further subset on Day 28. | PK population with available data | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | | Day 1 and Day 28 predose and 1, 2 , 4, 8, and 24 hours postdose | | | | ID | Title | Description |
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| OG000 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG001 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.4 mg | Participants received 0.4 mg naldemedine orally once daily for 28 days. |
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| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-emergent adverse events (TEAEs) were adverse events that occurred after the first dose of study drug. Treatment-related TEAEs were defined as TEAEs that were considered by the Investigator to be definitely, probably, or possibly related to study drug. | Adverse events were assessed using the safety population. The safety population included all participants who received study drug. This population was analyzed as treated. | Posted | | Number | | participants | | From first dose of study drug through 28 days after the last dose of study treatment (up to 57 days). | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo orally once daily for 28 days. | | OG001 | Naldemedine 0.1 mg | Participants received 0.1 mg naldemedine orally once daily for 28 days. | | OG002 | Naldemedine 0.2 mg | Participants received 0.2 mg naldemedine orally once daily for 28 days. | | OG003 | Naldemedine 0.4 mg | |
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