Trial Outcomes & Findings for Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 Versus Trisulfate Solution Using 2-Day Split-Dosing Regimen in Adults (NCT NCT02254486)
NCT ID: NCT02254486
Last Updated: 2018-05-15
Results Overview
The overall quality of bowel cleansing was assessed by a blinded central reader (an experienced and trained colonoscopist) using the segmental scores of the Harefield Cleansing Scale (HCS). A final HCS grading of A, B, C or D was derived. Grades A and B are classified as successful (i.e., all mucosa could be visualised) and C and D are classified as unsuccessful. Comparison of overall success of cleansing with NER1006 versus Trisulfate solution was evaluated using a non-inferiority study design.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
621 participants
Primary outcome timeframe
Two days (from day of first dosing to day of colonoscopy)
Results posted on
2018-05-15
Participant Flow
The trial recruited out/in-patients at 12 medical centres in the USA, from September 2014 to May 2015.
Participant milestones
| Measure |
Trisulfate Solution 2-Day Split-Dosing
Trisulfate solution: Trisulfate solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
NER1006 2-Day Split-Dosing
NER1006: NER1006 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
|---|---|---|
|
Overall Study
STARTED
|
311
|
310
|
|
Overall Study
COMPLETED
|
261
|
255
|
|
Overall Study
NOT COMPLETED
|
50
|
55
|
Reasons for withdrawal
| Measure |
Trisulfate Solution 2-Day Split-Dosing
Trisulfate solution: Trisulfate solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
NER1006 2-Day Split-Dosing
NER1006: NER1006 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
4
|
|
Overall Study
Protocol Violation
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
17
|
15
|
|
Overall Study
GFR<60mL/min
|
16
|
21
|
|
Overall Study
Various
|
12
|
12
|
Baseline Characteristics
Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 Versus Trisulfate Solution Using 2-Day Split-Dosing Regimen in Adults
Baseline characteristics by cohort
| Measure |
Trisulfate Solution 2-Day Split-Dosing
n=311 Participants
Trisulfate solution: Trisulfate solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
NER1006 2-Day Split-Dosing
n=310 Participants
NER1006: NER1006 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
Total
n=621 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
238 Participants
n=5 Participants
|
243 Participants
n=7 Participants
|
481 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
72 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
139 Participants
n=5 Participants
|
|
Age, Continuous
|
57.3 Years
STANDARD_DEVIATION 10.56 • n=5 Participants
|
57.7 Years
STANDARD_DEVIATION 10.36 • n=7 Participants
|
57.5 Years
STANDARD_DEVIATION 10.44 • n=5 Participants
|
|
Sex: Female, Male
Female
|
142 Participants
n=5 Participants
|
152 Participants
n=7 Participants
|
294 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
169 Participants
n=5 Participants
|
158 Participants
n=7 Participants
|
327 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Two days (from day of first dosing to day of colonoscopy)Population: The overall number of participants analyzed was based on the mFAS. This included all randomized patients, except any patient who (i) was randomized but subsequently failed to meet entry criteria and (ii) in whom it was confirmed (from their patient diary) that the same patient did not receive any study drug.
The overall quality of bowel cleansing was assessed by a blinded central reader (an experienced and trained colonoscopist) using the segmental scores of the Harefield Cleansing Scale (HCS). A final HCS grading of A, B, C or D was derived. Grades A and B are classified as successful (i.e., all mucosa could be visualised) and C and D are classified as unsuccessful. Comparison of overall success of cleansing with NER1006 versus Trisulfate solution was evaluated using a non-inferiority study design.
Outcome measures
| Measure |
Trisulfate Solution 2-Day Split-Dosing
n=280 Participants
Trisulfate solution: Trisulfate solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
NER1006 2-Day Split-Dosing
n=276 Participants
NER1006: NER1006 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
|---|---|---|
|
Number of Patients With Successful Bowel Cleansing (Overall Colon)
Successful
|
238 Participants
|
235 Participants
|
|
Number of Patients With Successful Bowel Cleansing (Overall Colon)
Failure
|
42 Participants
|
41 Participants
|
PRIMARY outcome
Timeframe: Two days (from day of first dosing to day of colonoscopy)Population: The overall number of participants analyzed was based on the mFAS. This included all randomized patients, except any patient who (i) was randomized but subsequently failed to meet entry criteria and (ii) in whom it was confirmed (from their patient diary) that the same patient did not receive any study drug.
The overall quality of bowel cleansing was assessed by a blinded central reader (an experienced and trained colonoscopist) using the segmental scores of the Harefield Cleansing Scale (HCS). Highly effective cleansing in the colon ascendens corresponded to scores 3 (Good) or 4 (Excellent) of the HCS. Adequate plus failure of cleansing corresponded to score 0-2. Comparison of 'Excellent plus good' cleansing of the colon ascendens using NER1006 versus Trisulfate Solution was evaluated using a non-inferiority study design.
Outcome measures
| Measure |
Trisulfate Solution 2-Day Split-Dosing
n=280 Participants
Trisulfate solution: Trisulfate solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
NER1006 2-Day Split-Dosing
n=276 Participants
NER1006: NER1006 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
|---|---|---|
|
Number of Patients With 'Excellent Plus Good' (Highly Effective) Bowel Cleansing (Colon Ascendens)
Excellent plus good
|
82 Participants
|
99 Participants
|
|
Number of Patients With 'Excellent Plus Good' (Highly Effective) Bowel Cleansing (Colon Ascendens)
Adequate plus failure
|
198 Participants
|
177 Participants
|
SECONDARY outcome
Timeframe: Two days (from day of first dosing to day of colonoscopy)Population: The overall number of participants analyzed was based on the mFAS. This included all randomized patients, except any patient who (i) was randomized but subsequently failed to meet entry criteria and (ii) in whom it was confirmed (from their patient diary) that the same patient did not receive any study drug
Comparison of the number of patients with at least one adenoma detected in the colon ascendens when NER1006 is used for bowel cleansing versus Trisulfate Solution. Adenoma detection rate (ADR) defined as the number of patients with at least one adenoma in the colon ascendens.
Outcome measures
| Measure |
Trisulfate Solution 2-Day Split-Dosing
n=280 Participants
Trisulfate solution: Trisulfate solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
NER1006 2-Day Split-Dosing
n=276 Participants
NER1006: NER1006 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
|---|---|---|
|
Adenoma Detection Rate (Colon Ascendens)
Patients with no adenomas detected
|
232 Participants
|
237 Participants
|
|
Adenoma Detection Rate (Colon Ascendens)
Patients with at least one adenoma detected
|
48 Participants
|
39 Participants
|
SECONDARY outcome
Timeframe: Two days (from day of first dosing to day of colonoscopy)Population: The overall number of participants analyzed was based on the mFAS. This included all randomized patients, except any patient who (i) was randomized but subsequently failed to meet entry criteria and (ii) in whom it was confirmed (from their patient diary) that the same patient did not receive any study drug.
Comparison of the number of patients with at least one adenoma detected in the overall colon when NER1006 is used for bowel cleansing versus Trisulfate Solution. ADR defined as the number of patients with at least one adenoma in the overall colon.
Outcome measures
| Measure |
Trisulfate Solution 2-Day Split-Dosing
n=280 Participants
Trisulfate solution: Trisulfate solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
NER1006 2-Day Split-Dosing
n=276 Participants
NER1006: NER1006 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
|---|---|---|
|
Adenoma Detection Rate (Overall Colon)
Patients with no adenomas detected
|
182 Participants
|
183 Participants
|
|
Adenoma Detection Rate (Overall Colon)
Patients with at least one adenoma detected
|
98 Participants
|
93 Participants
|
SECONDARY outcome
Timeframe: Two days (from day of first dosing to day of colonoscopy)Population: The overall number of participants analyzed was based on the mFAS. This included all randomized patients, except any patient who (i) was randomized but subsequently failed to meet entry criteria and (ii) in whom it was confirmed (from their patient diary) that the same patient did not receive any study drug.
Comparison of the number of patients with at least one polyp detected in the colon ascendens when NER1006 is used for bowel cleansing versus Trisulfate Solution. Polyp detection rate (PDR) defined as the number of patients with at least one polyp in the colon ascendens.
Outcome measures
| Measure |
Trisulfate Solution 2-Day Split-Dosing
n=280 Participants
Trisulfate solution: Trisulfate solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
NER1006 2-Day Split-Dosing
n=276 Participants
NER1006: NER1006 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
|---|---|---|
|
Polyp Detection Rate (Colon Ascendens)
Patients with no polyps detected
|
213 Participants
|
225 Participants
|
|
Polyp Detection Rate (Colon Ascendens)
Patients with at least one polyp detected
|
67 Participants
|
51 Participants
|
SECONDARY outcome
Timeframe: Two days (from day of first dosing to day of colonoscopy)Population: The overall number of participants analyzed was based on the mFAS. This included all randomized patients, except any patient who (i) was randomized but subsequently failed to meet entry criteria and (ii) in whom it was confirmed (from their patient diary) that the same patient did not receive any study drug.
Comparison of the number of patients with at least one polyp detected in the overall colon when NER1006 is used for bowel cleansing versus Trisulfate Solution. PDR defined as the number of patients with at least one polyp in the overall colon.
Outcome measures
| Measure |
Trisulfate Solution 2-Day Split-Dosing
n=280 Participants
Trisulfate solution: Trisulfate solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
NER1006 2-Day Split-Dosing
n=276 Participants
NER1006: NER1006 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
|---|---|---|
|
Polyp Detection Rate (Overall Colon)
Patients with no polyps detected
|
144 Participants
|
150 Participants
|
|
Polyp Detection Rate (Overall Colon)
Patients with at least one polyp detected
|
136 Participants
|
126 Participants
|
Adverse Events
Trisulfate Solution 2-Day Split-Dosing
Serious events: 1 serious events
Other events: 32 other events
Deaths: 0 deaths
NER1006 2-Day Split-Dosing
Serious events: 1 serious events
Other events: 73 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Trisulfate Solution 2-Day Split-Dosing
n=265 participants at risk
Trisulfate solution: Trisulfate solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
NER1006 2-Day Split-Dosing
n=262 participants at risk
NER1006: NER1006 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
|---|---|---|
|
Gastrointestinal disorders
Gastrintestinal haemorrhage
|
0.38%
1/265 • Number of events 1 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
0.00%
0/262 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/265 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
0.38%
1/262 • Number of events 1 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
Other adverse events
| Measure |
Trisulfate Solution 2-Day Split-Dosing
n=265 participants at risk
Trisulfate solution: Trisulfate solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
NER1006 2-Day Split-Dosing
n=262 participants at risk
NER1006: NER1006 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Distension
|
0.75%
2/265 • Number of events 2 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
1.1%
3/262 • Number of events 3 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
|
Gastrointestinal disorders
Abdominal Tenderness
|
0.38%
1/265 • Number of events 1 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
2.3%
6/262 • Number of events 7 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
|
Gastrointestinal disorders
Gastritis
|
1.1%
3/265 • Number of events 3 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
1.1%
3/262 • Number of events 3 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.38%
1/265 • Number of events 1 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
1.1%
3/262 • Number of events 3 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
|
Gastrointestinal disorders
Nausea
|
1.9%
5/265 • Number of events 6 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
6.9%
18/262 • Number of events 19 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
|
Gastrointestinal disorders
Vomiting
|
2.6%
7/265 • Number of events 8 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
6.1%
16/262 • Number of events 16 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
|
Investigations
Glomerular filtration rate decreased
|
1.9%
5/265 • Number of events 5 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
1.5%
4/262 • Number of events 4 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.38%
1/265 • Number of events 1 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
3.1%
8/262 • Number of events 8 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
|
Nervous system disorders
Headache
|
0.75%
2/265 • Number of events 2 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
1.9%
5/262 • Number of events 5 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
|
Infections and infestations
Nasopharyngitis
|
0.75%
2/265 • Number of events 2 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
1.1%
3/262 • Number of events 3 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
|
General disorders
Fatigue
|
1.1%
3/265 • Number of events 3 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
1.5%
4/262 • Number of events 4 • Afternoon of Day 1 (first dose) to Day 9 (final clinic visit)
Safety analyses were based on the safety population which included all randomized patients for whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=527). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and neither of the serious TEAEs was related to treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place