Trial Outcomes & Findings for Study Evaluating Subcutaneous MOA-728 for the Treatment of Opioid-Induced Constipation (OIC) in Subjects With Chronic Non-Malignant Pain (NCT NCT00529087)
NCT ID: NCT00529087
Last Updated: 2019-11-25
Results Overview
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).
COMPLETED
PHASE3
460 participants
up to 4 hours
2019-11-25
Participant Flow
Patients were recruited worldwide from August 2007 to September 2008.
Patients were screened up to 16 days.
Participant milestones
| Measure |
MOA-728 QD (Double-blind)
MOA-728 12 mg once daily (QD) for weeks 1 through 4
|
MOA-728 QOD (Double-blind)
MOA-728 12 mg once every other day, Placebo once daily on alternating days for weeks 1 through 4
|
Placebo (Double-blind)
Once daily for weeks 1 through 4
|
|---|---|---|---|
|
Overall Study
STARTED
|
150
|
148
|
162
|
|
Overall Study
COMPLETED
|
122
|
120
|
146
|
|
Overall Study
NOT COMPLETED
|
28
|
28
|
16
|
Reasons for withdrawal
| Measure |
MOA-728 QD (Double-blind)
MOA-728 12 mg once daily (QD) for weeks 1 through 4
|
MOA-728 QOD (Double-blind)
MOA-728 12 mg once every other day, Placebo once daily on alternating days for weeks 1 through 4
|
Placebo (Double-blind)
Once daily for weeks 1 through 4
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
10
|
13
|
4
|
|
Overall Study
Lost to Follow-up
|
6
|
4
|
1
|
|
Overall Study
Protocol Violation
|
8
|
7
|
6
|
|
Overall Study
Withdrawal by Subject
|
3
|
3
|
3
|
|
Overall Study
Protocol deviation
|
1
|
1
|
2
|
Baseline Characteristics
Study Evaluating Subcutaneous MOA-728 for the Treatment of Opioid-Induced Constipation (OIC) in Subjects With Chronic Non-Malignant Pain
Baseline characteristics by cohort
| Measure |
MOA-728 QD (Double-blind)
n=150 Participants
MOA-728 12 mg once daily (QD) for weeks 1 through 4
|
MOA-728 QOD (Double-blind)
n=148 Participants
MOA-728 12 mg once every other day, Placebo once daily on alternating days for weeks 1 through 4
|
Placebo (Double-blind)
n=162 Participants
Once daily for weeks 1 through 4
|
Total
n=460 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
47.99 years
STANDARD_DEVIATION 10.74 • n=5 Participants
|
48.64 years
STANDARD_DEVIATION 11.05 • n=7 Participants
|
49.69 years
STANDARD_DEVIATION 10.77 • n=5 Participants
|
48.79 years
STANDARD_DEVIATION 10.85 • n=4 Participants
|
|
Sex: Female, Male
Female
|
93 Participants
n=5 Participants
|
85 Participants
n=7 Participants
|
99 Participants
n=5 Participants
|
277 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
57 Participants
n=5 Participants
|
63 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
183 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: up to 4 hoursPopulation: 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).
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).
Outcome measures
| Measure |
MOA-728 QOD
n=162 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
Once daily
|
MOA-728 QD
n=298 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
Percentage of Patients Having a Rescue-free Bowel Movement (RFBM) Within 4 Hours of the First Dose
|
9.9 percentage of participants
|
—
|
34.2 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article.
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.
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
n=162 Participants
Once daily
|
|---|---|---|---|---|
|
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
|
9.3 percentage of active injections
Standard Deviation 12.6
|
28.9 percentage of active injections
Standard Deviation 26.2
|
9.4 percentage of active injections
Standard Deviation 11.3
|
SECONDARY outcome
Timeframe: up to 24 hoursPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article.
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.
Outcome measures
| Measure |
MOA-728 QOD
n=162 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
Once daily
|
MOA-728 QD
n=298 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
Time to the First Rescue-free Bowel Movement (RFBM) After First Dose
|
25.3 % of subjects achieving RFBM in 24 hours
0.5
|
—
|
46.0 % of subjects achieving RFBM in 24 hours
0.9
|
—
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF).
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.
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
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
|
1.5 bowel movements
Standard Error 0.2
|
3.1 bowel movements
Standard Error 0.2
|
—
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Patients who continued into the open-label period and received at least 1 dose of test article. Observed case analysis.
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.
Outcome measures
| Measure |
MOA-728 QOD
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
Once daily
|
MOA-728 QD
n=356 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
Weekly Number of Rescue-free Bowel Movements (RFBM) (Open-label Period)
|
—
|
—
|
3.7 bowel movements
Standard Deviation 2.0
|
—
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article.
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.
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
Percentage of Patients Achieving at Least 3 Rescue-free Bowel Movements (RFBM) Per Week in Double-blind Period
|
45.3 percentage of participants
|
38.3 percentage of participants
|
58.7 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Within 1-6 hours during 4 week double-blind periodPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF).
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.
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
n=162 Participants
Once daily
|
|---|---|---|---|---|
|
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
|
3.3 percentage of active injections
Standard Deviation 5.5
|
17.8 percentage of active injections
Standard Deviation 21.1
|
3.2 percentage of active injections
Standard Deviation 5.9
|
|
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
|
5.8 percentage of active injections
Standard Deviation 8.5
|
24.2 percentage of active injections
Standard Deviation 24.7
|
5.4 percentage of active injections
Standard Deviation 9.1
|
|
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
|
7.8 percentage of active injections
Standard Deviation 9.9
|
27.0 percentage of active injections
Standard Deviation 25.8
|
7.5 percentage of active injections
Standard Deviation 10.7
|
|
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
|
11.5 percentage of active injections
Standard Deviation 13.1
|
31.1 percentage of active injections
Standard Deviation 26.1
|
11.1 percentage of active injections
Standard Deviation 14.9
|
SECONDARY outcome
Timeframe: Within 1-6 hours during 4-week double-blind periodPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF).
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).
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
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
|
3.3 percentage of injections
Standard Deviation 5.5
|
17.8 percentage of injections
Standard Deviation 21.1
|
—
|
|
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
|
5.8 percentage of injections
Standard Deviation 8.5
|
24.2 percentage of injections
Standard Deviation 24.7
|
—
|
|
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
|
7.8 percentage of injections
Standard Deviation 9.9
|
27.0 percentage of injections
Standard Deviation 25.8
|
—
|
|
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 19.0
|
9.4 percentage of injections
Standard Deviation 11.3
|
28.9 percentage of injections
Standard Deviation 26.2
|
—
|
|
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
|
11.5 percentage of injections
Standard Deviation 13.1
|
31.1 percentage of injections
Standard Deviation 26.1
|
—
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
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.
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
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
|
37.7 percentage of participants
|
58.7 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
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.
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
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
|
54.9 percentage of participants
|
74.7 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
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.
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
Change in Weekly Number of Bowel Movements During Double-blind Period
|
1.7 bowel movements
Standard Error 0.2
|
1.3 bowel movements
Standard Error 0.2
|
2.7 bowel movements
Standard Error 0.2
|
—
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
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).
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
Change From Baseline in Weekly Number of Quality Rescue-free Bowel Movements (RFBM)
|
1.7 bowel movements
Standard Error 0.2
|
1.3 bowel movements
Standard Error 0.2
|
2.4 bowel movements
Standard Error 0.2
|
—
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
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.
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
Change in Weekly Number of Complete Rescue-free Bowel Movements (RFBM)
|
1.2 bowel movements
Standard Error 0.1
|
0.8 bowel movements
Standard Error 0.1
|
1.9 bowel movements
Standard Error 0.1
|
—
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
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.)
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
Change in Bristol Stool Form Scale Score for Rescue-free Bowel Movements (RFBM)
|
1.2 units on scale
Standard Error 0.1
|
0.9 units on scale
Standard Error 0.1
|
1.4 units on scale
Standard Error 0.1
|
—
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
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.
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
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
|
-0.8 units on scale
Standard Error 0.1
|
-1.1 units on scale
Standard Error 0.1
|
—
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Patients who continued into the open-label period and received at least 1 dose of test article.
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.)
Outcome measures
| Measure |
MOA-728 QOD
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
Once daily
|
MOA-728 QD
n=361 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
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 outcome
Timeframe: 8 weeksPopulation: Patients who continued into the open-label period and received at least 1 dose of test article.
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.
Outcome measures
| Measure |
MOA-728 QOD
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
Once daily
|
MOA-728 QD
n=361 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
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 outcome
Timeframe: 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
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.
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
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
|
17.6 percentage change
Standard Error 2.3
|
18.7 percentage change
Standard Error 2.4
|
—
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
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.
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
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
|
6.1 percentage change
Standard Error 1.7
|
11.7 percentage change
Standard Error 1.8
|
—
|
SECONDARY outcome
Timeframe: weeks 5-12Population: Patients who continued into the open-label period and received at least 1 dose of test article.
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.
Outcome measures
| Measure |
MOA-728 QOD
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
Once daily
|
MOA-728 QD
n=361 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
Percentage of Patients With Any Diarrhea or Watery Rescue-free Bowel Movements (RFBM) During Open-label Period.
|
—
|
—
|
50.1 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
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.
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
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
|
24.5 percentage change
Standard Error 2.7
|
31.5 percentage change
Standard Error 2.8
|
—
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Patients who were randomized and received at least 1 dose of double-blinded test article. Last observation carried forward (LOCF)
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.
Outcome measures
| Measure |
MOA-728 QOD
n=148 Participants
MOA-728 12 mg once every other day (QOD), Placebo once daily on alternating days
|
Placebo
n=162 Participants
Once daily
|
MOA-728 QD
n=150 Participants
MOA-728 12 mg once daily (QD)
|
Placebo QD
Once daily
|
|---|---|---|---|---|
|
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
|
19.9 percentage change
Standard Error 2.5
|
27.4 percentage change
Standard Error 2.6
|
—
|
Adverse Events
MOA-728 QD (Double-blind)
MOA-728 QOD (Double-blind)
Placebo (Double-blind)
MOA-728 PRN (Open-label)
Serious adverse events
| Measure |
MOA-728 QD (Double-blind)
n=150 participants at risk
MOA-728 12 mg once daily (QD) for weeks 1 through 4
|
MOA-728 QOD (Double-blind)
n=148 participants at risk
MOA-728 12 mg once every other day, Placebo once daily on alternating days for weeks 1 through 4
|
Placebo (Double-blind)
n=162 participants at risk
Once daily for weeks 1 through 4
|
MOA-728 PRN (Open-label)
n=364 participants at risk
MOA-728 12 mg as needed (PRN) for weeks 5 through 12
|
|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.00%
0/150
|
0.00%
0/148
|
0.00%
0/162
|
0.27%
1/364
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/150
|
0.00%
0/148
|
0.00%
0/162
|
0.27%
1/364
|
|
Nervous system disorders
Myoclonus
|
0.67%
1/150
|
0.00%
0/148
|
0.00%
0/162
|
0.00%
0/364
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/150
|
0.00%
0/148
|
0.00%
0/162
|
0.27%
1/364
|
|
Cardiac disorders
Extrasystoles
|
0.00%
0/150
|
0.68%
1/148
|
0.00%
0/162
|
0.00%
0/364
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/150
|
0.00%
0/148
|
0.62%
1/162
|
0.00%
0/364
|
|
Gastrointestinal disorders
Pancreatitis
|
0.67%
1/150
|
0.00%
0/148
|
0.00%
0/162
|
0.00%
0/364
|
|
Infections and infestations
Pneumonia
|
0.67%
1/150
|
0.00%
0/148
|
0.00%
0/162
|
0.27%
1/364
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.67%
1/150
|
0.00%
0/148
|
0.00%
0/162
|
0.00%
0/364
|
|
Investigations
White blood cell count increased
|
0.67%
1/150
|
0.00%
0/148
|
0.00%
0/162
|
0.00%
0/364
|
|
Metabolism and nutrition disorders
Dehydration
|
0.67%
1/150
|
0.00%
0/148
|
0.00%
0/162
|
0.00%
0/364
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.67%
1/150
|
0.00%
0/148
|
0.00%
0/162
|
0.00%
0/364
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/150
|
0.00%
0/148
|
0.62%
1/162
|
0.00%
0/364
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
0.67%
1/150
|
0.00%
0/148
|
0.00%
0/162
|
0.00%
0/364
|
|
Vascular disorders
Hypertension
|
0.00%
0/150
|
0.00%
0/148
|
0.00%
0/162
|
0.27%
1/364
|
Other adverse events
| Measure |
MOA-728 QD (Double-blind)
n=150 participants at risk
MOA-728 12 mg once daily (QD) for weeks 1 through 4
|
MOA-728 QOD (Double-blind)
n=148 participants at risk
MOA-728 12 mg once every other day, Placebo once daily on alternating days for weeks 1 through 4
|
Placebo (Double-blind)
n=162 participants at risk
Once daily for weeks 1 through 4
|
MOA-728 PRN (Open-label)
n=364 participants at risk
MOA-728 12 mg as needed (PRN) for weeks 5 through 12
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
0.67%
1/150
|
2.0%
3/148
|
0.62%
1/162
|
0.82%
3/364
|
|
Gastrointestinal disorders
Abdominal pain
|
19.3%
29/150
|
15.5%
23/148
|
3.7%
6/162
|
7.1%
26/364
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.3%
2/150
|
5.4%
8/148
|
2.5%
4/162
|
1.6%
6/364
|
|
Gastrointestinal disorders
Diarrhoea
|
6.0%
9/150
|
11.5%
17/148
|
3.7%
6/162
|
2.7%
10/364
|
|
Gastrointestinal disorders
Flatulence
|
4.7%
7/150
|
0.00%
0/148
|
3.7%
6/162
|
1.9%
7/364
|
|
Gastrointestinal disorders
Nausea
|
8.7%
13/150
|
11.5%
17/148
|
6.2%
10/162
|
4.1%
15/364
|
|
Gastrointestinal disorders
Vomiting
|
0.67%
1/150
|
7.4%
11/148
|
4.9%
8/162
|
1.4%
5/364
|
|
General disorders
Chills
|
1.3%
2/150
|
2.0%
3/148
|
0.00%
0/162
|
0.27%
1/364
|
|
General disorders
Feeling cold
|
0.00%
0/150
|
2.0%
3/148
|
0.00%
0/162
|
0.00%
0/364
|
|
General disorders
Feeling of body temperature change
|
0.00%
0/150
|
2.7%
4/148
|
0.62%
1/162
|
0.27%
1/364
|
|
General disorders
Oedema peripheral
|
0.67%
1/150
|
0.68%
1/148
|
2.5%
4/162
|
0.55%
2/364
|
|
Infections and infestations
Urinary tract infection
|
1.3%
2/150
|
2.0%
3/148
|
1.2%
2/162
|
4.1%
15/364
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.3%
2/150
|
2.0%
3/148
|
1.2%
2/162
|
1.9%
7/364
|
|
Nervous system disorders
Dizziness
|
3.3%
5/150
|
1.4%
2/148
|
0.62%
1/162
|
1.4%
5/364
|
|
Nervous system disorders
Headache
|
4.0%
6/150
|
3.4%
5/148
|
2.5%
4/162
|
2.5%
9/364
|
|
Nervous system disorders
Tremor
|
1.3%
2/150
|
3.4%
5/148
|
0.62%
1/162
|
0.82%
3/364
|
|
Psychiatric disorders
Anxiety
|
2.0%
3/150
|
2.0%
3/148
|
1.9%
3/162
|
0.27%
1/364
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
1.3%
2/150
|
2.0%
3/148
|
1.2%
2/162
|
1.6%
6/364
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
6.0%
9/150
|
6.1%
9/148
|
1.2%
2/162
|
2.2%
8/364
|
|
Skin and subcutaneous tissue disorders
Piloerection
|
0.67%
1/150
|
2.7%
4/148
|
0.00%
0/162
|
0.00%
0/364
|
|
Vascular disorders
Hot flush
|
2.7%
4/150
|
3.4%
5/148
|
1.9%
3/162
|
1.4%
5/364
|
|
Vascular disorders
Orthostatic hypotension
|
2.0%
3/150
|
0.68%
1/148
|
1.2%
2/162
|
0.55%
2/364
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER