Constipation
Conditions
Keywords
Opioid-Induced Constipation
Brief summary
The primary purpose of the protocol is to evaluate the safety, efficacy, and tolerability of subcutaneous MOA-728 versus placebo in subjects with chronic non-malignant pain who have Opioid-Induced Constipation (OIC).
Interventions
Subcutaneous
OTHERplacebo
placebo
Sponsors
Progenics Pharmaceuticals, Inc.
Bausch Health Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult outpatients with opioid-induced constipation and chronic non-malignant pain. * Taking oral, transdermal, intravenous, or subcutaneous opioids. * Willingness to discontinue all pre-study laxative therapy and use only study permitted rescue laxatives.
Exclusion criteria
* History of chronic constipation before the initiation of opioid therapy. * Other GI disorders known to affect bowel transit. * Women who are pregnant, breast-feeding, or plan to become pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Having a Rescue-free Bowel Movement (RFBM) Within 4 Hours of the First Dose | up to 4 hours | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). |
| Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 4 Hours of Injection During the Double-blind Period | 4 weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). Active injections are those that contain study drug (e.g., daily injections in MOA-728 QD treatment group and every other injection for the MOA-728 QOD treatment group). The corresponding injections in the placebo group were used as controls. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weekly Number of Rescue-free Bowel Movements (RFBM) (Open-label Period) | 8 weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The weekly number of RFBM was defined as the total number of RFBMs reported during study period divided by the number of days the patient reported diary information in that period, and then multiplied by 7 to normalize to a weekly number. Weekly number of RFBM determined as missing for \<4 days of information. |
| Percentage of Patients Achieving at Least 3 Rescue-free Bowel Movements (RFBM) Per Week in Double-blind Period | 4 weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The weekly number of RFBM was defined as the total number of RFBM reported during the study week divided by the number of days the patient reported diary information in that period, and then multiplied by 7 to normalize to a weekly number. |
| Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | Within 1-6 hours during 4 week double-blind period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). Active injections are those that contain study drug (e.g., daily injections in MOA-728 QD treatment group and every other injection for the MOA-728 QOD treatment group). The corresponding injections in the placebo group were used as controls. |
| Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | Within 1-6 hours during 4-week double-blind period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). |
| Percentage of Patients With a Weekly Rescue-free Bowel Movement (RFBM) Rate ≥ 3 and an Increase of at Least 1 in the Weekly RFBM Rate From Baseline for the Double-blind Period | 4 weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The weekly RFBM rate was defined as the total number of RFBM reported during study period divided by the number of days the subject reported diary information in that period, and then multiplied by 7 to normalize to a weekly rate. |
| Percentage of Patients With an Increase of at Least 1 in the Weekly Rescue-free Bowel Movement (RFBM) Rate From Baseline for the Double-blind Period at 4 Weeks | Baseline and 4 weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The weekly RFBM rate was defined as the total number of RFBM reported during study period divided by the number of days the subject reported diary information in that period, and then multiplied by 7 to normalize to a weekly rate. |
| Change in Weekly Number of Bowel Movements During Double-blind Period | 4 weeks | Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The weekly number of BM was defined as the total number of BMs reported during study period divided by the number of days the subject reported diary information in that period, and then multiplied by 7 to normalize to a weekly number. |
| Change From Baseline in Weekly Number of Quality Rescue-free Bowel Movements (RFBM) | 4 weeks | RFBM defined as bowel movement with no laxatives during the prior 24 hours. Information on laxative use, bowel movements and assessments were reported daily by patient. Weekly number of quality RFBM was the total number of quality RFBM reported in study period divided by number of days with information and multiplied by 7 for a normalized weekly number. Stool quality assessed with the Bristol Stool Form Scale (7-points) (1=difficult to pass, 7=entirely liquid). A quality RFBM defined as one other than diarrhea (Bristol Type 1-5). |
| Change in Weekly Number of Complete Rescue-free Bowel Movements (RFBM) | 4 weeks | A rescue-free bowel movement defined as a bowel movement with no laxatives use during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were reported daily by patient using a telephone interactive voice response system (IVRS). Weekly number of complete RFBM was the total number of complete RFBM reported in study period divided by the number of days with information, and multiplied by 7 for a normalized weekly number. A complete RFBM has a sensation of complete evacuation. |
| Time to the First Rescue-free Bowel Movement (RFBM) After First Dose | up to 24 hours | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). Responses following first injection were censored at 24 hours or at time of the second injection, which ever occurred first. |
| Change in Straining Scale Score of Rescue-free Bowel Movements (RFBM) From Baseline During Double-blind Period | 4 weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The amount of straining associated with bowel movements was assessed using a 5-point straining scale, where 0=none and 4=very severe. |
| Percentage of Patients With Improvement in Bristol Stool Form Scale Score for Rescue-free Bowel Movements (RFBM) by 1 Point During Open Label Period | 8 weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1 = separate hard lumps like nuts (difficult to pass) and Type 7 = watery, no solid pieces (entirely liquid.) |
| Percentage of Patients With Improvement in Straining Scale Score for Rescue-free Bowel Movements (RFBM) by 1 Point During Open Label Period | 8 weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The amount of straining associated with bowel movements was assessed using a 5-point straining scale, where 0=none and 4=very severe. |
| Change in Percentage of Rescue-free Bowel Movements (RFBM) With Bristol Stool Form Scale in Type 3 or Type 4 From Baseline During Double-blind Period | 4 weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1=separate hard lumps like nuts (difficult to pass) and Type 7=watery, no solid pieces (entirely liquid.) Specifically, Type 3=like a sausage but with cracks on the surface, Type 4=Like a sausage or snake, smooth and soft. |
| Change in Percentage of Rescue-free Bowel Movements (RFBM) Classified as Diarrhea or Watery Stools From Baseline During Double-blind Period | 4 weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1 = separate hard lumps like nuts (difficult to pass), Type 6 = fluffy pieces with ragged edges, a mushy stool, and Type 7 = watery, no solid pieces (entirely liquid.) This analysis included types 6 and 7. |
| Percentage of Patients With Any Diarrhea or Watery Rescue-free Bowel Movements (RFBM) During Open-label Period. | weeks 5-12 | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1 = separate hard lumps like nuts (difficult to pass), Type 6 = fluffy pieces with ragged edges, a mushy stool, and Type 7 = watery, no solid pieces (entirely liquid.) This analysis included types 6 and 7. |
| Change in Percentage of Rescue-free Bowel Movements (RFBM) With Straining Scale Scores of 0 or 1 (no, or Mild) From Baseline During Double-blind Period | 4 weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The amount of straining associated with bowel movements was assessed using a 5-point straining scale, where 0=none, 1 = mild and 4=very severe. |
| Change in Percentage of Rescue-free Bowel Movements (RFBM) With a Sensation of Complete Evacuation From Baseline During Double-blind Period | 4 weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). A complete RFBM has a sensation of complete evacuation. |
| Change in Bristol Stool Form Scale Score for Rescue-free Bowel Movements (RFBM) | 4 weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1 = separate hard lumps like nuts (difficult to pass) and Type 7 = watery, no solid pieces (entirely liquid.) |
| Change From Baseline in Weekly Number of Rescue-free Bowel Movements (RFBM) for the Double-blind Period at 4 Weeks | Baseline and 4 weeks | A rescue-free bowel movement defined as a bowel movement with no laxatives use during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were reported daily by patient using a telephone interactive voice response system (IVRS). The weekly number of RFBM was defined as the total number of RFBM reported during the double-blind period divided by the number of days the patient reported diary information in that period, and then multiplied by 7 to normalize to a weekly number. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited worldwide from August 2007 to September 2008.
Pre-assignment details
Patients were screened up to 16 days.
Participants by arm
| Arm | Count |
|---|---|
| MOA-728 QD (Double-blind) MOA-728 12 mg once daily (QD) for weeks 1 through 4 | 150 |
| MOA-728 QOD (Double-blind) MOA-728 12 mg once every other day, Placebo once daily on alternating days for weeks 1 through 4 | 148 |
| Placebo (Double-blind) Once daily for weeks 1 through 4 | 162 |
| Total | 460 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 13 | 4 |
| Overall Study | Lost to Follow-up | 6 | 4 | 1 |
| Overall Study | Protocol deviation | 1 | 1 | 2 |
| Overall Study | Protocol Violation | 8 | 7 | 6 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 3 |
Baseline characteristics
| Characteristic | MOA-728 QD (Double-blind) | MOA-728 QOD (Double-blind) | Placebo (Double-blind) | Total |
|---|---|---|---|---|
| Age, Continuous | 47.99 years STANDARD_DEVIATION 10.74 | 48.64 years STANDARD_DEVIATION 11.05 | 49.69 years STANDARD_DEVIATION 10.77 | 48.79 years STANDARD_DEVIATION 10.85 |
| Sex: Female, Male Female | 93 Participants | 85 Participants | 99 Participants | 277 Participants |
| Sex: Female, Male Male | 57 Participants | 63 Participants | 63 Participants | 183 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 74 / 150 | 67 / 148 | 62 / 162 | 137 / 364 |
| serious Total, serious adverse events | 5 / 150 | 1 / 148 | 2 / 162 | 4 / 364 |
Outcome results
Primary
Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 4 Hours of Injection During the Double-blind Period
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). Active injections are those that contain study drug (e.g., daily injections in MOA-728 QD treatment group and every other injection for the MOA-728 QOD treatment group). The corresponding injections in the placebo group were used as controls.
Time frame: 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 4 Hours of Injection During the Double-blind Period | 28.9 percentage of active injections | Standard Deviation 26.2 |
| Placebo | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 4 Hours of Injection During the Double-blind Period | 30.2 percentage of active injections | Standard Deviation 27.9 |
| Placebo QD (Only QOD Injections) | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 4 Hours of Injection During the Double-blind Period | 9.3 percentage of active injections | Standard Deviation 12.6 |
| Placebo QD | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 4 Hours of Injection During the Double-blind Period | 9.4 percentage of active injections | Standard Deviation 11.3 |
p-value: <0.00195% CI: [15.1, 24]t-test, 2 sided
p-value: <0.00195% CI: [16.1, 25.7]t-test, 2 sided
Primary
Percentage of Patients Having a Rescue-free Bowel Movement (RFBM) Within 4 Hours of the First Dose
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS).
Time frame: up to 4 hours
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. For this analysis, the MOA-728 QD and MOA-728 QOD treatment groups were combined as the treatment regimen was the same through the first dose (day 1).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MOA-728 QD and MOA-728 QOD | Percentage of Patients Having a Rescue-free Bowel Movement (RFBM) Within 4 Hours of the First Dose | 34.2 percentage of participants |
| Placebo | Percentage of Patients Having a Rescue-free Bowel Movement (RFBM) Within 4 Hours of the First Dose | 9.9 percentage of participants |
p-value: <0.00195% CI: [17.3, 31.4]Chi-squared
Secondary
Change From Baseline in Weekly Number of Quality Rescue-free Bowel Movements (RFBM)
RFBM defined as bowel movement with no laxatives during the prior 24 hours. Information on laxative use, bowel movements and assessments were reported daily by patient. Weekly number of quality RFBM was the total number of quality RFBM reported in study period divided by number of days with information and multiplied by 7 for a normalized weekly number. Stool quality assessed with the Bristol Stool Form Scale (7-points) (1=difficult to pass, 7=entirely liquid). A quality RFBM defined as one other than diarrhea (Bristol Type 1-5).
Time frame: 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Change From Baseline in Weekly Number of Quality Rescue-free Bowel Movements (RFBM) | 2.4 bowel movements | Standard Error 0.2 |
| Placebo | Change From Baseline in Weekly Number of Quality Rescue-free Bowel Movements (RFBM) | 1.7 bowel movements | Standard Error 0.2 |
| Placebo QD (Only QOD Injections) | Change From Baseline in Weekly Number of Quality Rescue-free Bowel Movements (RFBM) | 1.3 bowel movements | Standard Error 0.2 |
p-value: <0.00195% CI: [0.6, 1.5]ANCOVA
p-value: <0.00195% CI: [0, 0.9]ANCOVA
Secondary
Change From Baseline in Weekly Number of Rescue-free Bowel Movements (RFBM) for the Double-blind Period at 4 Weeks
A rescue-free bowel movement defined as a bowel movement with no laxatives use during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were reported daily by patient using a telephone interactive voice response system (IVRS). The weekly number of RFBM was defined as the total number of RFBM reported during the double-blind period divided by the number of days the patient reported diary information in that period, and then multiplied by 7 to normalize to a weekly number.
Time frame: Baseline and 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Change From Baseline in Weekly Number of Rescue-free Bowel Movements (RFBM) for the Double-blind Period at 4 Weeks | 3.1 bowel movements | Standard Error 0.2 |
| Placebo | Change From Baseline in Weekly Number of Rescue-free Bowel Movements (RFBM) for the Double-blind Period at 4 Weeks | 2.1 bowel movements | Standard Error 0.2 |
| Placebo QD (Only QOD Injections) | Change From Baseline in Weekly Number of Rescue-free Bowel Movements (RFBM) for the Double-blind Period at 4 Weeks | 1.5 bowel movements | Standard Error 0.2 |
p-value: <0.00195% CI: [1.1, 2.1]ANCOVA
p-value: 0.01195% CI: [0.2, 1.2]ANCOVA
Secondary
Change in Bristol Stool Form Scale Score for Rescue-free Bowel Movements (RFBM)
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1 = separate hard lumps like nuts (difficult to pass) and Type 7 = watery, no solid pieces (entirely liquid.)
Time frame: 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Change in Bristol Stool Form Scale Score for Rescue-free Bowel Movements (RFBM) | 1.4 units on scale | Standard Error 0.1 |
| Placebo | Change in Bristol Stool Form Scale Score for Rescue-free Bowel Movements (RFBM) | 1.2 units on scale | Standard Error 0.1 |
| Placebo QD (Only QOD Injections) | Change in Bristol Stool Form Scale Score for Rescue-free Bowel Movements (RFBM) | 0.9 units on scale | Standard Error 0.1 |
p-value: 0.00295% CI: [0.2, 0.7]ANCOVA
p-value: 0.11995% CI: [-0.1, 0.5]ANCOVA
Secondary
Change in Percentage of Rescue-free Bowel Movements (RFBM) Classified as Diarrhea or Watery Stools From Baseline During Double-blind Period
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1 = separate hard lumps like nuts (difficult to pass), Type 6 = fluffy pieces with ragged edges, a mushy stool, and Type 7 = watery, no solid pieces (entirely liquid.) This analysis included types 6 and 7.
Time frame: 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Change in Percentage of Rescue-free Bowel Movements (RFBM) Classified as Diarrhea or Watery Stools From Baseline During Double-blind Period | 11.7 percentage change | Standard Error 1.8 |
| Placebo | Change in Percentage of Rescue-free Bowel Movements (RFBM) Classified as Diarrhea or Watery Stools From Baseline During Double-blind Period | 8.8 percentage change | Standard Error 1.8 |
| Placebo QD (Only QOD Injections) | Change in Percentage of Rescue-free Bowel Movements (RFBM) Classified as Diarrhea or Watery Stools From Baseline During Double-blind Period | 6.1 percentage change | Standard Error 1.7 |
p-value: 0.02395% CI: [0.8, 10.4]ANCOVA
p-value: 0.25895% CI: [-2, 7.6]ANCOVA
Secondary
Change in Percentage of Rescue-free Bowel Movements (RFBM) With a Sensation of Complete Evacuation From Baseline During Double-blind Period
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). A complete RFBM has a sensation of complete evacuation.
Time frame: 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Change in Percentage of Rescue-free Bowel Movements (RFBM) With a Sensation of Complete Evacuation From Baseline During Double-blind Period | 27.4 percentage change | Standard Error 2.6 |
| Placebo | Change in Percentage of Rescue-free Bowel Movements (RFBM) With a Sensation of Complete Evacuation From Baseline During Double-blind Period | 24.2 percentage change | Standard Error 2.6 |
| Placebo QD (Only QOD Injections) | Change in Percentage of Rescue-free Bowel Movements (RFBM) With a Sensation of Complete Evacuation From Baseline During Double-blind Period | 19.9 percentage change | Standard Error 2.5 |
p-value: 0.03895% CI: [0.4, 14.7]ANCOVA
p-value: 0.23795% CI: [-2.8, 11.5]ANCOVA
Secondary
Change in Percentage of Rescue-free Bowel Movements (RFBM) With Bristol Stool Form Scale in Type 3 or Type 4 From Baseline During Double-blind Period
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1=separate hard lumps like nuts (difficult to pass) and Type 7=watery, no solid pieces (entirely liquid.) Specifically, Type 3=like a sausage but with cracks on the surface, Type 4=Like a sausage or snake, smooth and soft.
Time frame: 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Change in Percentage of Rescue-free Bowel Movements (RFBM) With Bristol Stool Form Scale in Type 3 or Type 4 From Baseline During Double-blind Period | 18.7 percentage change | Standard Error 2.4 |
| Placebo | Change in Percentage of Rescue-free Bowel Movements (RFBM) With Bristol Stool Form Scale in Type 3 or Type 4 From Baseline During Double-blind Period | 18.5 percentage change | Standard Error 2.4 |
| Placebo QD (Only QOD Injections) | Change in Percentage of Rescue-free Bowel Movements (RFBM) With Bristol Stool Form Scale in Type 3 or Type 4 From Baseline During Double-blind Period | 17.6 percentage change | Standard Error 2.3 |
p-value: 0.73195% CI: [-5.4, 7.7]ANCOVA
p-value: 0.77995% CI: [-5.6, 7.5]ANCOVA
Secondary
Change in Percentage of Rescue-free Bowel Movements (RFBM) With Straining Scale Scores of 0 or 1 (no, or Mild) From Baseline During Double-blind Period
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The amount of straining associated with bowel movements was assessed using a 5-point straining scale, where 0=none, 1 = mild and 4=very severe.
Time frame: 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Change in Percentage of Rescue-free Bowel Movements (RFBM) With Straining Scale Scores of 0 or 1 (no, or Mild) From Baseline During Double-blind Period | 31.5 percentage change | Standard Error 2.8 |
| Placebo | Change in Percentage of Rescue-free Bowel Movements (RFBM) With Straining Scale Scores of 0 or 1 (no, or Mild) From Baseline During Double-blind Period | 31.1 percentage change | Standard Error 2.8 |
| Placebo QD (Only QOD Injections) | Change in Percentage of Rescue-free Bowel Movements (RFBM) With Straining Scale Scores of 0 or 1 (no, or Mild) From Baseline During Double-blind Period | 24.5 percentage change | Standard Error 2.7 |
p-value: 0.07195% CI: [-0.6, 14.5]ANCOVA
p-value: 0.08795% CI: [-1, 14.2]ANCOVA
Secondary
Change in Straining Scale Score of Rescue-free Bowel Movements (RFBM) From Baseline During Double-blind Period
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The amount of straining associated with bowel movements was assessed using a 5-point straining scale, where 0=none and 4=very severe.
Time frame: 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Change in Straining Scale Score of Rescue-free Bowel Movements (RFBM) From Baseline During Double-blind Period | -1.1 units on scale | Standard Error 0.1 |
| Placebo | Change in Straining Scale Score of Rescue-free Bowel Movements (RFBM) From Baseline During Double-blind Period | -1.1 units on scale | Standard Error 0.1 |
| Placebo QD (Only QOD Injections) | Change in Straining Scale Score of Rescue-free Bowel Movements (RFBM) From Baseline During Double-blind Period | -0.8 units on scale | Standard Error 0.1 |
p-value: 0.00895% CI: [-0.5, -0.1]ANCOVA
p-value: 0.01595% CI: [-0.5, 0]ANCOVA
Secondary
Change in Weekly Number of Bowel Movements During Double-blind Period
Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The weekly number of BM was defined as the total number of BMs reported during study period divided by the number of days the subject reported diary information in that period, and then multiplied by 7 to normalize to a weekly number.
Time frame: 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Change in Weekly Number of Bowel Movements During Double-blind Period | 2.7 bowel movements | Standard Error 0.2 |
| Placebo | Change in Weekly Number of Bowel Movements During Double-blind Period | 1.7 bowel movements | Standard Error 0.2 |
| Placebo QD (Only QOD Injections) | Change in Weekly Number of Bowel Movements During Double-blind Period | 1.3 bowel movements | Standard Error 0.2 |
p-value: <0.00195% CI: [1, 1.9]ANCOVA
p-value: 0.10295% CI: [-0.1, 0.8]ANCOVA
Secondary
Change in Weekly Number of Complete Rescue-free Bowel Movements (RFBM)
A rescue-free bowel movement defined as a bowel movement with no laxatives use during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were reported daily by patient using a telephone interactive voice response system (IVRS). Weekly number of complete RFBM was the total number of complete RFBM reported in study period divided by the number of days with information, and multiplied by 7 for a normalized weekly number. A complete RFBM has a sensation of complete evacuation.
Time frame: 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Change in Weekly Number of Complete Rescue-free Bowel Movements (RFBM) | 1.9 bowel movements | Standard Error 0.1 |
| Placebo | Change in Weekly Number of Complete Rescue-free Bowel Movements (RFBM) | 1.2 bowel movements | Standard Error 0.1 |
| Placebo QD (Only QOD Injections) | Change in Weekly Number of Complete Rescue-free Bowel Movements (RFBM) | 0.8 bowel movements | Standard Error 0.1 |
p-value: <0.00195% CI: [0.8, 1.6]ANCOVA
p-value: 0.01295% CI: [0.1, 0.9]ANCOVA
Secondary
Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). Active injections are those that contain study drug (e.g., daily injections in MOA-728 QD treatment group and every other injection for the MOA-728 QOD treatment group). The corresponding injections in the placebo group were used as controls.
Time frame: Within 1-6 hours during 4 week double-blind period
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 3 hours | 27.0 percentage of active injections | Standard Deviation 25.8 |
| MOA-728 QD and MOA-728 QOD | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 6 hours | 31.1 percentage of active injections | Standard Deviation 26.1 |
| MOA-728 QD and MOA-728 QOD | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 1 hour | 17.8 percentage of active injections | Standard Deviation 21.1 |
| MOA-728 QD and MOA-728 QOD | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 2 hours | 24.2 percentage of active injections | Standard Deviation 24.7 |
| Placebo | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 2 hours | 24.1 percentage of active injections | Standard Deviation 26.4 |
| Placebo | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 3 hours | 28.0 percentage of active injections | Standard Deviation 27.5 |
| Placebo | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 6 hours | 32.5 percentage of active injections | Standard Deviation 28.5 |
| Placebo | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 1 hour | 17.3 percentage of active injections | Standard Deviation 22.6 |
| Placebo QD (Only QOD Injections) | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 2 hours | 5.8 percentage of active injections | Standard Deviation 8.5 |
| Placebo QD (Only QOD Injections) | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 1 hour | 3.3 percentage of active injections | Standard Deviation 5.5 |
| Placebo QD (Only QOD Injections) | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 3 hours | 7.8 percentage of active injections | Standard Deviation 9.9 |
| Placebo QD (Only QOD Injections) | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 6 hours | 11.5 percentage of active injections | Standard Deviation 13.1 |
| Placebo QD | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 6 hours | 11.1 percentage of active injections | Standard Deviation 14.9 |
| Placebo QD | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 2 hours | 5.4 percentage of active injections | Standard Deviation 9.1 |
| Placebo QD | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 3 hours | 7.5 percentage of active injections | Standard Deviation 10.7 |
| Placebo QD | Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | 1 hour | 3.2 percentage of active injections | Standard Deviation 5.9 |
Comparison: The statistical analysis for all time points (1, 2, 3 and 6 hours) is only shown once as the p value is the same for all time points.p-value: <0.001t-test, 2 sided
Comparison: The statistical analysis for all time points (1, 2, 3 and 6 hours) is only shown once as the p value is the same for all time points.p-value: <0.001t-test, 2 sided
Secondary
Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS).
Time frame: Within 1-6 hours during 4-week double-blind period
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 6 hours | 31.1 percentage of injections | Standard Deviation 26.1 |
| MOA-728 QD and MOA-728 QOD | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 4 hours | 28.9 percentage of injections | Standard Deviation 26.2 |
| MOA-728 QD and MOA-728 QOD | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 2 hours | 24.2 percentage of injections | Standard Deviation 24.7 |
| MOA-728 QD and MOA-728 QOD | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 1 hour | 17.8 percentage of injections | Standard Deviation 21.1 |
| MOA-728 QD and MOA-728 QOD | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 3 hours | 27.0 percentage of injections | Standard Deviation 25.8 |
| Placebo | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 1 hour | 11.3 percentage of injections | Standard Deviation 15.3 |
| Placebo | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 6 hours | 22.2 percentage of injections | Standard Deviation 19.3 |
| Placebo | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 2 hours | 16.2 percentage of injections | Standard Deviation 18.2 |
| Placebo | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 4 hours | 20.4 percentage of injections | Standard Deviation 19 |
| Placebo | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 3 hours | 18.7 percentage of injections | Standard Deviation 18.8 |
| Placebo QD (Only QOD Injections) | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 6 hours | 11.5 percentage of injections | Standard Deviation 13.1 |
| Placebo QD (Only QOD Injections) | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 2 hours | 5.8 percentage of injections | Standard Deviation 8.5 |
| Placebo QD (Only QOD Injections) | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 3 hours | 7.8 percentage of injections | Standard Deviation 9.9 |
| Placebo QD (Only QOD Injections) | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 4 hours | 9.4 percentage of injections | Standard Deviation 11.3 |
| Placebo QD (Only QOD Injections) | Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | 1 hour | 3.3 percentage of injections | Standard Deviation 5.5 |
Comparison: 1 hourp-value: <0.00195% CI: [11.2, 17.9]ANOVA
Comparison: 1 hourp-value: <0.00195% CI: [4.6, 11.4]ANOVA
Comparison: 2 hoursp-value: <0.00195% CI: [14.4, 22.5]ANOVA
Comparison: 2 hoursp-value: <0.00195% CI: [6.3, 14.5]ANOVA
Comparison: 3 hoursp-value: <0.00195% CI: [15, 23.5]ANOVA
Comparison: 3 hoursp-value: <0.00195% CI: [6.7, 15.3]ANOVA
Comparison: 4 hoursp-value: <0.00195% CI: [15.2, 23.9]ANOVA
Comparison: 4 hoursp-value: <0.00195% CI: [6.6, 15.4]ANOVA
Comparison: 6 hoursp-value: <0.00195% CI: [15.2, 24.1]ANOVA
Comparison: 6 hoursp-value: <0.00195% CI: [6.2, 15.2]ANOVA
Secondary
Percentage of Patients Achieving at Least 3 Rescue-free Bowel Movements (RFBM) Per Week in Double-blind Period
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The weekly number of RFBM was defined as the total number of RFBM reported during the study week divided by the number of days the patient reported diary information in that period, and then multiplied by 7 to normalize to a weekly number.
Time frame: 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MOA-728 QD and MOA-728 QOD | Percentage of Patients Achieving at Least 3 Rescue-free Bowel Movements (RFBM) Per Week in Double-blind Period | 58.7 percentage of participants |
| Placebo | Percentage of Patients Achieving at Least 3 Rescue-free Bowel Movements (RFBM) Per Week in Double-blind Period | 45.3 percentage of participants |
| Placebo QD (Only QOD Injections) | Percentage of Patients Achieving at Least 3 Rescue-free Bowel Movements (RFBM) Per Week in Double-blind Period | 38.3 percentage of participants |
p-value: <0.00195% CI: [9.5, 31.3]Chi-squared
p-value: 0.21295% CI: [-4, 18]Chi-squared
Secondary
Percentage of Patients With an Increase of at Least 1 in the Weekly Rescue-free Bowel Movement (RFBM) Rate From Baseline for the Double-blind Period at 4 Weeks
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The weekly RFBM rate was defined as the total number of RFBM reported during study period divided by the number of days the subject reported diary information in that period, and then multiplied by 7 to normalize to a weekly rate.
Time frame: Baseline and 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MOA-728 QD and MOA-728 QOD | Percentage of Patients With an Increase of at Least 1 in the Weekly Rescue-free Bowel Movement (RFBM) Rate From Baseline for the Double-blind Period at 4 Weeks | 74.7 percentage of participants |
| Placebo | Percentage of Patients With an Increase of at Least 1 in the Weekly Rescue-free Bowel Movement (RFBM) Rate From Baseline for the Double-blind Period at 4 Weeks | 68.2 percentage of participants |
| Placebo QD (Only QOD Injections) | Percentage of Patients With an Increase of at Least 1 in the Weekly Rescue-free Bowel Movement (RFBM) Rate From Baseline for the Double-blind Period at 4 Weeks | 54.9 percentage of participants |
p-value: <0.00195% CI: [9.4, 30.1]Chi-squared
p-value: 0.01695% CI: [2.6, 24]Chi-squared
Secondary
Percentage of Patients With Any Diarrhea or Watery Rescue-free Bowel Movements (RFBM) During Open-label Period.
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1 = separate hard lumps like nuts (difficult to pass), Type 6 = fluffy pieces with ragged edges, a mushy stool, and Type 7 = watery, no solid pieces (entirely liquid.) This analysis included types 6 and 7.
Time frame: weeks 5-12
Population: Patients who continued into the open-label period and received at least 1 dose of test article.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MOA-728 QD and MOA-728 QOD | Percentage of Patients With Any Diarrhea or Watery Rescue-free Bowel Movements (RFBM) During Open-label Period. | 50.1 percentage of participants |
Secondary
Percentage of Patients With a Weekly Rescue-free Bowel Movement (RFBM) Rate ≥ 3 and an Increase of at Least 1 in the Weekly RFBM Rate From Baseline for the Double-blind Period
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The weekly RFBM rate was defined as the total number of RFBM reported during study period divided by the number of days the subject reported diary information in that period, and then multiplied by 7 to normalize to a weekly rate.
Time frame: 4 weeks
Population: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MOA-728 QD and MOA-728 QOD | Percentage of Patients With a Weekly Rescue-free Bowel Movement (RFBM) Rate ≥ 3 and an Increase of at Least 1 in the Weekly RFBM Rate From Baseline for the Double-blind Period | 58.7 percentage of participants |
| Placebo | Percentage of Patients With a Weekly Rescue-free Bowel Movement (RFBM) Rate ≥ 3 and an Increase of at Least 1 in the Weekly RFBM Rate From Baseline for the Double-blind Period | 43.2 percentage of participants |
| Placebo QD (Only QOD Injections) | Percentage of Patients With a Weekly Rescue-free Bowel Movement (RFBM) Rate ≥ 3 and an Increase of at Least 1 in the Weekly RFBM Rate From Baseline for the Double-blind Period | 37.7 percentage of participants |
p-value: <0.00195% CI: [10.2, 31.9]Chi-squared
p-value: 0.31695% CI: [-5.3, 16.5]Chi-squared
Secondary
Percentage of Patients With Improvement in Bristol Stool Form Scale Score for Rescue-free Bowel Movements (RFBM) by 1 Point During Open Label Period
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1 = separate hard lumps like nuts (difficult to pass) and Type 7 = watery, no solid pieces (entirely liquid.)
Time frame: 8 weeks
Population: Patients who continued into the open-label period and received at least 1 dose of test article.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MOA-728 QD and MOA-728 QOD | Percentage of Patients With Improvement in Bristol Stool Form Scale Score for Rescue-free Bowel Movements (RFBM) by 1 Point During Open Label Period | 57.9 percentage of participants |
Secondary
Percentage of Patients With Improvement in Straining Scale Score for Rescue-free Bowel Movements (RFBM) by 1 Point During Open Label Period
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The amount of straining associated with bowel movements was assessed using a 5-point straining scale, where 0=none and 4=very severe.
Time frame: 8 weeks
Population: Patients who continued into the open-label period and received at least 1 dose of test article.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MOA-728 QD and MOA-728 QOD | Percentage of Patients With Improvement in Straining Scale Score for Rescue-free Bowel Movements (RFBM) by 1 Point During Open Label Period | 55.4 percentage of participants |
Secondary
Time to the First Rescue-free Bowel Movement (RFBM) After First Dose
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). Responses following first injection were censored at 24 hours or at time of the second injection, which ever occurred first.
Time frame: up to 24 hours
Population: Patients who were randomized and received at least 1 dose of double-blinded test article.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Time to the First Rescue-free Bowel Movement (RFBM) After First Dose | 46.0 % of subjects achieving RFBM in 24 hours | 0.9 |
| Placebo | Time to the First Rescue-free Bowel Movement (RFBM) After First Dose | 25.3 % of subjects achieving RFBM in 24 hours | 0.5 |
p-value: <0.001Log Rank
Secondary
Weekly Number of Rescue-free Bowel Movements (RFBM) (Open-label Period)
A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The weekly number of RFBM was defined as the total number of RFBMs reported during study period divided by the number of days the patient reported diary information in that period, and then multiplied by 7 to normalize to a weekly number. Weekly number of RFBM determined as missing for \<4 days of information.
Time frame: 8 weeks
Population: Patients who continued into the open-label period and received at least 1 dose of test article. Observed case analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOA-728 QD and MOA-728 QOD | Weekly Number of Rescue-free Bowel Movements (RFBM) (Open-label Period) | 3.7 bowel movements | Standard Deviation 2 |