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.
Study Details
Study Description
Brief Summary
This study evaluates the efficacy, safety and tolerability of NER1006 versus a sodium picosulfate and magnesium salt solution (SP + MS) in adult patients requiring bowel cleansing prior to any procedure that requires a clean bowel, using a Day Before Only Dosing regimen. Approximately 484 patients will be randomised with the aim of achieving a minimum of 220 patients in each of the 2 groups.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NER1006, Day Before-Only Dosing NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy). |
Drug: NER1006, Day Before-Only Dosing
The subject will self-administer both doses of NER1006 in the evening of Day 1 with 1-2 hours interval. Subject will take mandatory additional clear fluid after each dose.
|
| Active Comparator: 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). |
Drug: SP+MS, Day Before-Only Dosing
The subject will self-administer SP+MS in the morning of Day 1 and afternoon of Day 1. Subject will take mandatory additional clear fluid after each dose.
|
Outcome Measures
Primary Outcome Measures
- Number of Patients With Successful Bowel Cleansing (Overall Colon) [One day (day before colonoscopy)]
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.
- Number of Patients With 'Excellent Plus Good' (Highly Effective) Bowel Cleansing (Colon Ascendens) [One day (day before colonoscopy)]
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.
Secondary Outcome Measures
- Adenoma Detection Rate (Colon Ascendens) [One day (day before colonoscopy).]
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.
- Adenoma Detection Rate (Overall Colon) [One day (day before colonoscopy)]
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.
- Polyp Detection Rate (Colon Ascendens) [One day (day before colonoscopy)]
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.
- Polyp Detection Rate (Overall Colon) [One day (day before colonoscopy)]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must provide written informed consent.
-
Male and female outpatients and inpatients aged: ≥18 to ≤85 years undergoing a screening, surveillance or diagnostic colonoscopy.
-
Females of child-bearing potential must have a negative pregnancy test at Screening and at Visit 2 and must be practising one of the following methods of birth control and agree to continue with the regimen throughout the study period (unless postmenopausal or surgically sterile, or whose sole sexual partner has had a successful vasectomy):
-
Oral, implantable, or injectable contraceptives (for a minimum of three months before study entry) in combination with a condom;
-
Intrauterine device in combination with a condom;
-
Double barrier method (condom* and occlusive cap [diaphragm or cervical/vault caps] with spermicidal foam/gel/film/cream/suppository).
-
Willing, able and competent to complete the entire study and to comply with instructions.
Exclusion Criteria:
-
Patients with past history within last 12 months or current episode of severe constipation (requiring repeated use of laxatives/enema or physical intervention before resolution), known or suspected ileus, gastrointestinal obstruction, gastric retention, bowel perforation, toxic colitis or megacolon.
-
Patients with ongoing severe acute Inflammatory Bowel Disease.
-
Patients who have had previous significant gastrointestinal surgeries, including colonic resection, sub-total colectomy, abdomino-perineal resection, de-functioning colostomy, Hartmann's procedure and de-functioning ileostomy or other similar surgeries involving structure and function of the small or large colon.
-
Regular use of laxatives or colon motility altering drugs in the last month (i.e. more than 2-3 times per week) and/or laxative use within 72 hours prior to administration of the preparation.
-
Patients with active intestinal bleeding episodes or with a clinically significant low hemoglobin level <9 g/dL for women and <11 g/dL for men at screening.
-
Known glucose-6-phosphate dehydrogenase (G6PD) deficiency.
-
Known phenylketonuria.
-
Known hypersensitivity to polyethylene glycols, ascorbic acid and sulfates (not including sulfa-based products), sodium picosulfate and magnesium salt compounds, or any other component of the study drug or comparator
-
Past history within the last 12 months or evidence of any on-going clinically relevant electrocardiogram abnormalities (e.g. arrhythmias).
-
History of uncontrolled hypertension with systolic blood pressure >170 mmHg and diastolic blood pressure >100 mmHg.
-
Patients with cardiac insufficiency NYHA grades III or IV.
-
Patients with moderate to severe renal insufficiency (i.e. with GFR, <60 mL/min/1.73m2).
-
Patient with serum albumin <3.4 g/dL.
-
Patients with liver disease of grades B and C according to the Child Pugh classification.
-
Patients suffering from dehydration at screening as evaluated by the Investigator from physical examination and laboratory investigations.
-
Patients with clinically significant electrolyte abnormalities, whether pre-existing or noted at screening, such as hypernatremia, hyponatremia, hyperphosphatemia, hypermagnesemia, hypokalemia, hypocalcaemia, dehydration, or those secondary to the use of diuretics or angiotensin converting enzyme (ACE) inhibitors.
-
Patients with any other clinically significant hematological parameters including coagulation profile at screening.
-
Patients with impaired consciousness that might predispose them to pulmonary aspiration.
-
Patients undergoing colonoscopy for foreign body removal and/or decompression.
-
Patients who are pregnant or lactating, or intending to become pregnant during the study.
-
Clinically relevant findings on physical examination based on the Investigator's judgment.
-
History of drug or alcohol abuse within the 12 months prior to dosing.
-
Concurrent participation in an investigational drug or device study or participation within three months of study entry.
-
Patients who are ordered to live in an institution on court or authority order.
-
Patients with history of rhabdomyolysis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Charité - Campus Virchow Klinikum | Berlin | Germany | ||
| 2 | University Hospital Schleswig-Holstein | Kiel | Germany | 24105 | |
| 3 | An der Germania Brauerei 6 | Münster | Germany | ||
| 4 | An der Germania Brauerei 6 | Milan | Italy | ||
| 5 | Osp.San Raffaele U.O. Gastroenterologia | Milan | Italy | ||
| 6 | P.T.P.Nuovo Regina Margherita | Rome | Italy | ||
| 7 | Onze Lieve Vrouwe Gashuis | Amsterdam | Netherlands | ||
| 8 | Albert Schweitzer Ziekenhuis | Dordrecht | Netherlands | ||
| 9 | Radboud UMC | Nijmegen | Netherlands | ||
| 10 | Orbis Medisch Centrum | Sittard | Netherlands | ||
| 11 | Centrum Medyczne sw. Lukasza | Czestochowa | Poland | ||
| 12 | Instytut Medycyny Wsi im. Witolda Chodzki w | Lubliniec | Poland | ||
| 13 | Specjalistyczna Praktyka Lekarska dr med. Marek Horynski | Sopot | Poland | ||
| 14 | SPSK Nr 1 im. Prof. Tadeusza Sokolowskiego | Szczecin | Poland | ||
| 15 | Hospital de Vinalopó, Unidad de Endoscopia Digestiva | Elche | Spain | ||
| 16 | Hospital Universitario de la Princesa | Madrid | Spain | ||
| 17 | Hospital Universitario La Paz, Unidad Enfermedad Intestinal | Madrid | Spain | ||
| 18 | Department of Surgery, Raigmore Hospital | Inverness | United Kingdom | ||
| 19 | Derriford Hospital | Plymouth | United Kingdom |
Sponsors and Collaborators
- Norgine
Investigators
- Principal Investigator: Stefan Schreiber, University Hospital Schleswig-Holstein
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NER1006-03/2014 (DAYB)
Study Results
Participant Flow
| Recruitment Details | The trial recruited out/in-patients at 19 medical centres in Europe, from November 2014 to July 2015. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | SP+MS, Day Before-Only Dosing | NER1006, Day Before-Only Dosing |
|---|---|---|
| Arm/Group Description | SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy). | NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy). |
| Period Title: Overall Study | ||
| STARTED | 257 | 258 |
| COMPLETED | 240 | 233 |
| NOT COMPLETED | 17 | 25 |
Baseline Characteristics
| Arm/Group Title | SP+MS, Day Before-Only Dosing | NER1006, Day Before-Only Dosing | Total |
|---|---|---|---|
| Arm/Group Description | SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the moring of the day before colonoscopy). | NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy). | Total of all reporting groups |
| Overall Participants | 257 | 258 | 515 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
1
0.4%
|
1
0.2%
|
| Between 18 and 65 years |
207
80.5%
|
203
78.7%
|
410
79.6%
|
| >=65 years |
50
19.5%
|
54
20.9%
|
104
20.2%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
52.9
(13.35)
|
54.6
(11.64)
|
53.8
(12.50)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
174
67.7%
|
168
65.1%
|
342
66.4%
|
| Male |
83
32.3%
|
90
34.9%
|
173
33.6%
|
Outcome Measures
| Title | Number of Patients With Successful Bowel Cleansing (Overall Colon) |
|---|---|
| Description | 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. |
| Time Frame | One day (day before colonoscopy) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SP+MS, Day Before-Only Dosing | NER1006, Day Before-Only Dosing |
|---|---|---|
| Arm/Group Description | SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy). | NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy). |
| Measure Participants | 251 | 250 |
| Successful |
135
52.5%
|
155
60.1%
|
| Failure |
116
45.1%
|
95
36.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SP+MS, Day Before-Only Dosing, NER1006, Day Before-Only Dosing |
|---|---|---|
| Comments | The hypothesis was to demonstrate non-inferiority (NI) of NER1006 regimen to SP+MS (10% margin). Success rate was no. of patients with successful overall bowel cleansing as proportion of no. of patients in each group. Treatment effect was NER1006 success rate - SP+MS 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. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The confidence limits were adjusted for multiple comparisons (two alternative primary endpoints): To be declared non-inferior, the primary endpoint must show a difference in success rates of no greater than 10% in favor of SP+MS using lower 1-sided 97.5% confidence limits. Calculated using exact Clopper-Pearson confidence limits. | |
| Statistical Test of Hypothesis | p-Value | 0.038 |
| Comments | The p-value was adjusted for multiple comparisons (2 alternative primary endpoints): To be declared superior, the primary endpoint must demonstrate non-inferiority with 1-sided p-value <0.025, the threshold for statistical significance. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in success rate |
| Estimated Value | 8.22 | |
| Confidence Interval |
(1-Sided) 97.5% -0.50 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Patients With 'Excellent Plus Good' (Highly Effective) Bowel Cleansing (Colon Ascendens) |
|---|---|
| Description | 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. |
| Time Frame | One day (day before colonoscopy) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SP+MS, Day Before-Only Dosing | NER1006, Day Before-Only Dosing |
|---|---|---|
| Arm/Group Description | SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy). | NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy). |
| Measure Participants | 251 | 250 |
| Excellent plus good |
3
1.2%
|
11
4.3%
|
| Adequate plus failure |
248
96.5%
|
239
92.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SP+MS, Day Before-Only Dosing, NER1006, Day Before-Only Dosing |
|---|---|---|
| Comments | Hypothesis was to demonstrate NI of NER1006 regimen to SP+MS (10% margin). Success rate was no. of patients with highly effective cleansing of the colon ascendens as proportion of no. of patients in each group. Treatment effect was NER1006 success rate - SP+MS 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. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The confidence limits were adjusted for multiple comparisons (two alternative primary endpoints): To be declared non-inferior the primary endpoint must show a difference in success rates of no greater than 10% in favor of SP+MS using lower 1-sided 97.5% confidence limits. Calculated using exact Clopper-Pearson confidence limits. | |
| Statistical Test of Hypothesis | p-Value | 0.027 |
| Comments | The p-value was adjusted for multiple comparisons (2 alternative primary endpoints): To be declared superior, primary endpoint must demonstrate non-inferiority with 1-sided p-value <0.025, the threshold for statistical significance. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in excellent plus good rate |
| Estimated Value | 3.20 | |
| Confidence Interval |
(1-Sided) 97.5% -5.56 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adenoma Detection Rate (Colon Ascendens) |
|---|---|
| Description | 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. |
| Time Frame | One day (day before colonoscopy). |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SP+MS, Day Before-Only Dosing | NER1006, Day Before-Only Dosing |
|---|---|---|
| Arm/Group Description | SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy). | NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy). |
| Measure Participants | 251 | 250 |
| Patients with no adenomas detected |
241
93.8%
|
234
90.7%
|
| Patients with at least one adenoma detected |
10
3.9%
|
16
6.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SP+MS, Day Before-Only Dosing, NER1006, Day Before-Only Dosing |
|---|---|---|
| Comments | 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 - SP+MS 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. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | To be declared non-inferior, the key secondary endpoint must show a difference in rates of no greater than 10% in favor of SP+MS using lower 1-sided 97.5% confidence limits. Calculated using exact Clopper-Pearson confidence limits. | |
| Statistical Test of Hypothesis | p-Value | 0.154 |
| Comments | To be declared superior, the key secondary endpoint must demonstrate non-inferiority and show a significant advantage for NER1006 relative to SP+MS with 1-sided p-value <0.025, the threshold for statistical significance. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in ADR |
| Estimated Value | 2.42 | |
| Confidence Interval |
(2-Sided) 95% -6.35 to 11.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adenoma Detection Rate (Overall Colon) |
|---|---|
| Description | 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. |
| Time Frame | One day (day before colonoscopy) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | SP+MS, Day Before-Only Dosing | NER1006, Day Before-Only Dosing |
|---|---|---|
| Arm/Group Description | SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy). | NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy). |
| Measure Participants | 251 | 250 |
| Patients with no adenomas detected |
204
79.4%
|
195
75.6%
|
| Patients with at least one adenoma detected |
47
18.3%
|
55
21.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SP+MS, Day Before-Only Dosing, NER1006, Day Before-Only Dosing |
|---|---|---|
| Comments | 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 - SP+MS 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. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | To be declared non-inferior, the key secondary endpoint must show a difference in rates of no greater than 10% in favor of SP+MS using lower 1-sided 97.5% confidence limits. Calculated using exact Clopper-Pearson confidence limits. | |
| Statistical Test of Hypothesis | p-Value | 0.212 |
| Comments | To be declared superior, the key secondary endpoint must demonstrate non-inferiority and show a significant advantage for NER1006 relative to SP+MS with 1-sided p-value <0.025, the threshold for statistical significance. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in ADR |
| Estimated Value | 3.27 | |
| Confidence Interval |
(2-Sided) 95% -5.56 to 11.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Polyp Detection Rate (Colon Ascendens) |
|---|---|
| Description | 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. |
| Time Frame | One day (day before colonoscopy) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SP+MS, Day Before-Only Dosing | NER1006, Day Before-Only Dosing |
|---|---|---|
| Arm/Group Description | SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy). | NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy). |
| Measure Participants | 251 | 250 |
| Patients with no polyps detected |
232
90.3%
|
220
85.3%
|
| Patients with at least one polyp detected |
19
7.4%
|
30
11.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SP+MS, Day Before-Only Dosing, NER1006, Day Before-Only Dosing |
|---|---|---|
| Comments | 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 - SP+MS 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. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | To be declared non-inferior, the key secondary endpoint must show a difference in rates of no greater than 10% in favor of SP+MS using lower 1-sided 97.5% confidence limits. Calculated using exact Clopper-Pearson confidence limits. | |
| Statistical Test of Hypothesis | p-Value | 0.064 |
| Comments | To be declared superior, the key secondary endpoint must demonstrate non-inferiority and show a significant advantage for NER1006 relative to SP+MS with 1-sided p-value <0.025, the threshold for statistical significance. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in PDR |
| Estimated Value | 4.43 | |
| Confidence Interval |
(2-Sided) 95% -4.36 to 13.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Polyp Detection Rate (Overall Colon) |
|---|---|
| Description | 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. |
| Time Frame | One day (day before colonoscopy) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SP+MS, Day Before-Only Dosing | NER1006, Day Before-Only Dosing |
|---|---|---|
| Arm/Group Description | SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy). | NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy). |
| Measure Participants | 251 | 250 |
| Patients with no polyps detected |
160
62.3%
|
152
58.9%
|
| Patients with at least one polyp detected |
91
35.4%
|
98
38%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SP+MS, Day Before-Only Dosing, NER1006, Day Before-Only Dosing |
|---|---|---|
| Comments | 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 - SP+MS 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. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | To be declared non-inferior, the key secondary endpoint must show a difference in rates of no greater than 10% in favor of SP+MS using lower 1-sided 97.5% confidence limits. Calculated using exact Clopper-Pearson confidence limits. | |
| Statistical Test of Hypothesis | p-Value | 0.278 |
| Comments | To be declared superior, the key secondary endpoint must demonstrate non-inferiority and show a significant advantage for NER1006 relative to SP+MS with 1-sided p-value <0.025, the threshold for statistical significance. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in PDR |
| Estimated Value | 2.95 | |
| Confidence Interval |
(2-Sided) 95% -5.96 to 11.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Morning of Day 1 (first dose) to Day 9 (final clinic visit) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||
| Arm/Group Title | SP+MS, Day Before-Only Dosing | NER1006, Day Before-Only Dosing | ||
| Arm/Group Description | SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the morning of the day before colonoscopy). | NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy). | ||
All Cause Mortality |
||||
| SP+MS, Day Before-Only Dosing | NER1006, Day Before-Only Dosing | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/241 (0%) | 0/235 (0%) | ||
Serious Adverse Events |
||||
| SP+MS, Day Before-Only Dosing | NER1006, Day Before-Only Dosing | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/241 (0%) | 1/235 (0.4%) | ||
| Infections and infestations | ||||
| Ovarian abscess | 0/241 (0%) | 0 | 1/235 (0.4%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| SP+MS, Day Before-Only Dosing | NER1006, Day Before-Only Dosing | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/241 (3.7%) | 32/235 (13.6%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 3/241 (1.2%) | 3 | 8/235 (3.4%) | 8 |
| Nausea | 2/241 (0.8%) | 2 | 6/235 (2.6%) | 6 |
| Vomiting | 0/241 (0%) | 0 | 11/235 (4.7%) | 11 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/241 (0%) | 0 | 3/235 (1.3%) | 3 |
| Nervous system disorders | ||||
| Headache | 4/241 (1.7%) | 4 | 4/235 (1.7%) | 5 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Lucy Clayton |
|---|---|
| Organization | Norgine Ltd |
| Phone | +44-1895-826669 |
| LClayton@norgine.com |
- NER1006-03/2014 (DAYB)