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NER1006:2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)

Trisulfate Solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)

The subject will self-administer the first dose of the assigned investigational product in the evening prior to the scheduled colonoscopy and take mandatory additional clear fluid. Subject will take the second dose together with mandatory additional clear fluids on the morning of the colonoscopy.

NER1006

Trisulfate solution

Michael Demicco

This study evaluates the efficacy, safety and tolerability of NER1006 versus Trisulfate Solution (TS) in adult patients requiring bowel cleansing prior to any procedure that requires a clean bowel, using a 2-Day evening/morning Split-Dosing regimen. Approximately 540 patients will be randomised with the aim of achieving a minimum of 245 patients in each of the 2 groups.

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

A Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 (a Low Volume Bowel Cleansing Solution) Versus a Trisulfate Bowel Cleansing Solution Using 2-Day Split-Dosing Regimen in Adults

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.

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.

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.

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.

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.

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.

Norgine

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.

Trisulfate solution: Trisulfate solution 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)

Trisulfate Solution 2-Day Split-Dosing

NER1006: NER1006 2-Day Split-Dosing Regimen (to commence in the evening of the day before the colonoscopy)

NER1006 2-Day Split-Dosing

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

The number of participants for analysis, 245 per arm, was based on assumed overall cleansing success rates of 90% for both Trisulfate Solution (TS) and NER1006, a non-inferiority (NI) margin of 10%, and at least 90% power to demonstrate NI. The overall number of participants analyzed was based on the modified full analysis set (mFAS).

Imputation of failure occurred in 7% of patients. This strict analytical approach reduced the cleansing success rates for both treatments.

Lucy Clayton

The hypothesis was to demonstrate NI of NER1006 to Trisulfate Solution (TS) (10% margin). Success rate was number of patients with successful overall bowel cleansing as proportion of number of patients in each group. Treatment effect was NER1006 success rate - TS success rate. A Hochberg procedure was used to control Type I error since there were 2 alternative primary endpoints. An alpha level of 1.25% 1-sided was used. A closed testing procedure used to evaluate superiority if NI was met.

Successful

Failure

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.

Number of Patients With Successful Bowel Cleansing (Overall Colon)

Excellent plus good

Adequate plus failure

Number of Patients With 'Excellent Plus Good' (Highly Effective) Bowel Cleansing (Colon Ascendens)

If at least one of the alternative primary endpoints was met, then key secondary endpoints for the same colon region as met by the primary endpoint were evaluated hierarchically in a pre-specified order. The difference in ADR was calculated as NER1006 rate - TS rate using 1-sided 97.5% confidence limits. Formal testing was to proceed in the hierarchy if preceding key secondary endpoint met non-inferiority. This procedure ensured overall Type I error control at 2.5% 1-sided.

Patients with no adenomas detected

Patients with at least one adenoma detected

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

Adenoma Detection Rate (Colon Ascendens)

Adenoma Detection Rate (Overall Colon)

If at least one of the alternative primary endpoints was met, then key secondary endpoints for the same colon region as met by the primary endpoint were evaluated hierarchically in a pre-specified order. The difference in PDR was calculated as NER1006 rate - Trisulfate Solution rate using 1-sided 97.5% confidence limits. Formal testing was to proceed in the hierarchy if preceding key secondary endpoint met non-inferiority. This procedure ensured overall Type I error control at 2.5% 1-sided.

Patients with no polyps detected

Patients with at least one polyp detected

Polyp Detection Rate (Colon Ascendens)

If at least one of the alternative primary endpoints were met, then key secondary endpoints were evaluated hierarchichally in a pre-specified order. Non-inferiority was concluded if the 1-sided 97.5% confidence limit (CL) for difference in proportion of events between 2 groups excluded a 10% or greater difference was in favor of Trisulate Solution. Formal testing was to proceed in the hierarchy if preceding key secondary endpoint had at least met non-inferiority.

Spots Global Cancer Trial Database 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

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