Trial Outcomes & Findings for Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 Versus a Sodium Picosulfate and Magnesium Salt Solution Using Day Before-Only Dosing Regimen in Adults. (NCT NCT02273141)

NCT ID: NCT02273141

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 visualized) and C and D are classified as unsuccessful. Comparison of overall success of cleansing with NER1006 versus SP+MS was evaluated using a non-inferiority study design.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

515 participants

Primary outcome timeframe

One day (day before colonoscopy)

Results posted on

2018-05-15

Participant Flow

The trial recruited out/in-patients at 19 medical centres in Europe, from November 2014 to July 2015.

Participant milestones

Participant milestones
Measure
SP+MS, Day Before-Only Dosing
SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy).
NER1006, Day Before-Only Dosing
NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).
Overall Study
STARTED
257
258
Overall Study
COMPLETED
240
233
Overall Study
NOT COMPLETED
17
25

Reasons for withdrawal

Reasons for withdrawal
Measure
SP+MS, Day Before-Only Dosing
SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy).
NER1006, Day Before-Only Dosing
NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).
Overall Study
Adverse Event
0
1
Overall Study
Lost to Follow-up
1
3
Overall Study
Withdrawal by Subject
10
15
Overall Study
Various
6
6

Baseline Characteristics

Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 Versus a Sodium Picosulfate and Magnesium Salt Solution Using Day Before-Only Dosing Regimen in Adults.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
SP+MS, Day Before-Only Dosing
n=257 Participants
SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the moring of the day before colonoscopy).
NER1006, Day Before-Only Dosing
n=258 Participants
NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).
Total
n=515 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
207 Participants
n=5 Participants
203 Participants
n=7 Participants
410 Participants
n=5 Participants
Age, Categorical
>=65 years
50 Participants
n=5 Participants
54 Participants
n=7 Participants
104 Participants
n=5 Participants
Age, Continuous
52.9 years
STANDARD_DEVIATION 13.35 • n=5 Participants
54.6 years
STANDARD_DEVIATION 11.64 • n=7 Participants
53.8 years
STANDARD_DEVIATION 12.50 • n=5 Participants
Sex: Female, Male
Female
174 Participants
n=5 Participants
168 Participants
n=7 Participants
342 Participants
n=5 Participants
Sex: Female, Male
Male
83 Participants
n=5 Participants
90 Participants
n=7 Participants
173 Participants
n=5 Participants

PRIMARY outcome

Timeframe: One day (day before 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 visualized) and C and D are classified as unsuccessful. Comparison of overall success of cleansing with NER1006 versus SP+MS was evaluated using a non-inferiority study design.

Outcome measures

Outcome measures
Measure
SP+MS, Day Before-Only Dosing
n=251 Participants
SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy).
NER1006, Day Before-Only Dosing
n=250 Participants
NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).
Number of Patients With Successful Bowel Cleansing (Overall Colon)
Successful
135 Participants
155 Participants
Number of Patients With Successful Bowel Cleansing (Overall Colon)
Failure
116 Participants
95 Participants

PRIMARY outcome

Timeframe: One day (day before 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 SP+MS was evaluated using a non-inferiority study design.

Outcome measures

Outcome measures
Measure
SP+MS, Day Before-Only Dosing
n=251 Participants
SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy).
NER1006, Day Before-Only Dosing
n=250 Participants
NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).
Number of Patients With 'Excellent Plus Good' (Highly Effective) Bowel Cleansing (Colon Ascendens)
Excellent plus good
3 Participants
11 Participants
Number of Patients With 'Excellent Plus Good' (Highly Effective) Bowel Cleansing (Colon Ascendens)
Adequate plus failure
248 Participants
239 Participants

SECONDARY outcome

Timeframe: One day (day before 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 SP+MS. Adenoma detection rate (ADR) defined as the number of patients with at least one adenoma in the colon ascendens.

Outcome measures

Outcome measures
Measure
SP+MS, Day Before-Only Dosing
n=251 Participants
SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy).
NER1006, Day Before-Only Dosing
n=250 Participants
NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).
Adenoma Detection Rate (Colon Ascendens)
Patients with no adenomas detected
241 Participants
234 Participants
Adenoma Detection Rate (Colon Ascendens)
Patients with at least one adenoma detected
10 Participants
16 Participants

SECONDARY outcome

Timeframe: One day (day before colonoscopy)

Population: The overall number of participants analyzed was based on the mFAS. This included all randomized patients with the exception of any patient who was randomized but subsequently failed to meet entry criteria and in whom it was confirmed (from their patient diary) that the same patient did not receive any study drug (n=501).

Comparison of the number of patients with at least one adenoma detected in the overall colon when NER1006 is used for bowel cleansing versus SP+MS. Adenoma detection rate (ADR) defined as the number of patients with at least one adenoma in the overall colon.

Outcome measures

Outcome measures
Measure
SP+MS, Day Before-Only Dosing
n=251 Participants
SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy).
NER1006, Day Before-Only Dosing
n=250 Participants
NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).
Adenoma Detection Rate (Overall Colon)
Patients with no adenomas detected
204 Participants
195 Participants
Adenoma Detection Rate (Overall Colon)
Patients with at least one adenoma detected
47 Participants
55 Participants

SECONDARY outcome

Timeframe: One day (day before 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 SP+MS. Polyp detection rate (PDR) defined as the number of patients with at least one polyp in the colon ascendens.

Outcome measures

Outcome measures
Measure
SP+MS, Day Before-Only Dosing
n=251 Participants
SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy).
NER1006, Day Before-Only Dosing
n=250 Participants
NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).
Polyp Detection Rate (Colon Ascendens)
Patients with no polyps detected
232 Participants
220 Participants
Polyp Detection Rate (Colon Ascendens)
Patients with at least one polyp detected
19 Participants
30 Participants

SECONDARY outcome

Timeframe: One day (day before 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 SP+MS. Polyp detection rate (PDR) defined as the number of patients with at least one polyp in the overall colon.

Outcome measures

Outcome measures
Measure
SP+MS, Day Before-Only Dosing
n=251 Participants
SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy).
NER1006, Day Before-Only Dosing
n=250 Participants
NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).
Polyp Detection Rate (Overall Colon)
Patients with no polyps detected
160 Participants
152 Participants
Polyp Detection Rate (Overall Colon)
Patients with at least one polyp detected
91 Participants
98 Participants

Adverse Events

SP+MS, Day Before-Only Dosing

Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths

NER1006, Day Before-Only Dosing

Serious events: 1 serious events
Other events: 32 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
SP+MS, Day Before-Only Dosing
n=241 participants at risk
SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy).
NER1006, Day Before-Only Dosing
n=235 participants at risk
NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).
Infections and infestations
Ovarian abscess
0.00%
0/241 • Morning 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=476). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and the serious TEAE was not related to treatment.
0.43%
1/235 • Number of events 1 • Morning 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=476). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and the serious TEAE was not related to treatment.

Other adverse events

Other adverse events
Measure
SP+MS, Day Before-Only Dosing
n=241 participants at risk
SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy).
NER1006, Day Before-Only Dosing
n=235 participants at risk
NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).
Gastrointestinal disorders
Abdominal pain
1.2%
3/241 • Number of events 3 • Morning 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=476). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and the serious TEAE was not related to treatment.
3.4%
8/235 • Number of events 8 • Morning 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=476). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and the serious TEAE was not related to treatment.
Gastrointestinal disorders
Nausea
0.83%
2/241 • Number of events 2 • Morning 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=476). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and the serious TEAE was not related to treatment.
2.6%
6/235 • Number of events 6 • Morning 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=476). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and the serious TEAE was not related to treatment.
Gastrointestinal disorders
Vomiting
0.00%
0/241 • Morning 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=476). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and the serious TEAE was not related to treatment.
4.7%
11/235 • Number of events 11 • Morning 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=476). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and the serious TEAE was not related to treatment.
Metabolism and nutrition disorders
Dehydration
0.00%
0/241 • Morning 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=476). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and the serious TEAE was not related to treatment.
1.3%
3/235 • Number of events 3 • Morning 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=476). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and the serious TEAE was not related to treatment.
Nervous system disorders
Headache
1.7%
4/241 • Number of events 4 • Morning 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=476). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and the serious TEAE was not related to treatment.
1.7%
4/235 • Number of events 5 • Morning 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=476). The analyses are based on treatment emergent adverse events (TEAEs). There were no deaths and the serious TEAE was not related to treatment.

Additional Information

Lucy Clayton

Norgine Ltd

Phone: +44-1895-826669

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place