MORA: Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 Versus MOVIPREP® Using 2-Day Split-Dosing and 1-Day Morning Split-Dosing Regimen in Adults.
Sponsor
Norgine (Industry)
Overall Status
Completed
CT.gov ID
NCT02273167
Collaborator
(none)
849
29
3
10
29.3
2.9
Study Details
Study Description
Brief Summary
This study evaluates the efficacy, safety and tolerability of NER1006 versus MOVIPREP in adult patients requiring bowel cleansing prior to any procedure that requires a clean bowel, using a 2-Day evening/morning Split-Dosing and 1-Day morning only Split-Dosing regimens. Approximately 810 patients will be randomised with the aim of achieving a minimum of 245 patients in each of the 3 groups.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
849 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Investigator)
Primary Purpose:
Screening
Official Title:
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 MOVIPREP Using 2-Day Split-Dosing and 1-Day Morning Split-Dosing Regimen in Adults.
Study Start Date
:
Oct 1, 2014
Actual Primary Completion Date
:
Aug 1, 2015
Actual Study Completion Date
:
Aug 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NER1006, 2-Day Split-Dosing NER1006: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). |
Drug: NER1006, 2-Day Split-Dosing
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.
|
| Experimental: NER1006,1-Day Morning Split-Dosing NER1006: 1-Day Morning Split-Dosing Regimen (to commence in the morning of the day of colonoscopy). |
Drug: NER1006,1-Day Morning Split-Dosing
The subject will self-administer the first dose of the investigational product on the morning of the colonoscopy and take mandatory additional clear fluid.
After a 1-2 hour break the subject will self-administer the second dose plus additional clear mandatory fluid.
|
| Active Comparator: MOVIPREP, 2-Day Split-Dosing MOVIPREP®: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). |
Drug: MOVIPREP, 2-Day Split-Dosing
The subject will self-administer the first dose of the assigned investigational product in the evening prior to the scheduled colonoscopy and take recommended additional clear fluid. Subject will take the second dose together with recommended additional clear fluids on the morning of the colonoscopy.
|
Outcome Measures
Primary Outcome Measures
- Number of Patients With Successful Bowel Cleansing (Overall Colon) [Up to 2 days (from day of first dosing to day of 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 2-Day and 1-Day versus MOVIPREP was evaluated using a non-inferiority study design.
- Number of Patients With 'Excellent Plus Good' (Highly Effective) Bowel Cleansing (Colon Ascendens) [Up to 2 days (from day of first dosing to day of 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 2-Day and 1-Day versus MOVIPREP was evaluated using a non-inferiority study design.
Secondary Outcome Measures
- Adenoma Detection Rate (Colon Ascendens) [Up to 2 days (from day of first dosing to day of colonoscopy)]
Comparison of the number of patients with at least one adenoma detected in the colon ascendens when NER1006 2-Day and 1-Day is used for bowel cleansing versus MOVIPREP. Adenoma detection rate (ADR) defined as the number of patients with at least one adenoma in the colon ascendens.
- Adenoma Detection Rate (Overall Colon) [Up to 2 days (from day of first dosing to day of colonoscopy)]
Comparison of the number of patients with at least one adenoma detected in the overall colon when NER1006 2-Day and 1-Day is used for bowel cleansing versus MOVIPREP. Adenoma detection rate (ADR) defined as the number of patients with at least one adenoma in the overall colon.
- Polyp Detection Rate (Colon Ascendens) [Up to 2 days (from day of first dosing to day of colonoscopy)]
Comparison of the number of patients with at least one polyp detected in the colon ascendens when NER1006 2-Day and 1-Day is used for bowel cleansing versus MOVIPREP. Polyp detection rate (PDR) defined as the number of patients with at least one polyp in the colon ascendens.
- Polyp Detection Rate (Overall Colon) [Up to 2 days (from day of first dosing to day of 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 number detected when MOVIPREP is used. PDR defined as the number of patients with at least one polyp in the overall colon.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 and able 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) 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 (ECG) 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 severe renal insufficiency (i.e. with GFR, <30 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | AZ Sint-Lucas | Brugge | Belgium | ||
| 2 | UZ Ghent | Ghent | Belgium | ||
| 3 | UZ Leuven | Leuven | Belgium | 3000 Leuven | |
| 4 | CHC- Clinique Saint-Joseph | Liège | Belgium | ||
| 5 | Hôpital Avicenne- Service de Gastro-Entérologie | Bobigny | France | ||
| 6 | Hôpital Hotel-Dieu | Nantes | France | ||
| 7 | Kliniken Essen-Mitte; Abteilung für Gastroenterologie | Essen | Germany | ||
| 8 | Klinikum der Friedrich Schiller Universität Jena | Jena | Germany | ||
| 9 | Praxis für Innere Medizin, Gastroenterologie und Allg. Medizin | Ludwigshafen | Germany | ||
| 10 | A.O.U. di Bologna - Policlinico S. Orsola-Malpighi | Bologna | Italy | ||
| 11 | Ospedale Valduce U.O. Gastroenterologia e Endoscopia | Como | Italy | ||
| 12 | P.O. Maresca OORR Area Vesuviana ASL | Naples | Italy | ||
| 13 | Centro di Riferimento Oncologico (C.R.O.) S.O.C Gastroenterologia | Pordenone | Italy | ||
| 14 | Pol. Univ. A. Gemelli U.O. di Endoscopia Digestiva Chirurgica | Roma | Italy | ||
| 15 | Uniwersytecki Szpital Kliniczny w Bialymstoku | Białystok | Poland | ||
| 16 | Gabinet Internistyczny dr n. med. Krzysztof Janik | Czestochowa | Poland | ||
| 17 | Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych | Warsaw | Poland | ||
| 18 | Robert Petryka Gabinet Internistyczny | Warsaw | Poland | ||
| 19 | Lexmedica Durbajlo Hanna | Wrocław | Poland | ||
| 20 | NZOZ Centrum Medyczne-Szpital Swietej Rodziny | Łódź | Poland | ||
| 21 | Hospital General Universitario de Alicante | Alicante | Spain | ||
| 22 | Hospital del Mar | Barcelona | Spain | ||
| 23 | Hospital Universitari Germans Trias i Pujol | Barcelona | Spain | ||
| 24 | Hospital Clínico San Carlos | Madrid | Spain | ||
| 25 | Hospital Ramon y Cajal - Ctra. De Colmenar km. 9, 100 | Madrid | Spain | ||
| 26 | Lothian Health Board | Edinburgh | United Kingdom | ||
| 27 | Borders General Hospital | Melrose | United Kingdom | ||
| 28 | Royal Shrewsbury Hospital | Shrewsbury | United Kingdom | ||
| 29 | Royal Albert Edward Infirmary Department | Wigan | United Kingdom |
Sponsors and Collaborators
- Norgine
Investigators
- Principal Investigator: Raf Bisschops, MD, UZ Leuven
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Norgine
ClinicalTrials.gov Identifier:
NCT02273167
Other Study ID Numbers:
- NER1006-02/2014 (MORA)
First Posted:
Oct 23, 2014
Last Update Posted:
May 15, 2018
Last Verified:
Apr 1, 2018
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The trial recruited out/in-patients at 29 medical centres in Europe, from October 2014 to June 2015. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | MOVIPREP, 2-Day Split-Dosing | NER1006, 2-Day Split-Dosing | NER1006,1-Day Morning Split-Dosing |
|---|---|---|---|
| Arm/Group Description | MOVIPREP®: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 1-Day Morning Split-Dosing Regimen (to commence in the morning of the day of colonoscopy). |
| Period Title: Overall Study | |||
| STARTED | 283 | 283 | 283 |
| COMPLETED | 259 | 260 | 262 |
| NOT COMPLETED | 24 | 23 | 21 |
Baseline Characteristics
| Arm/Group Title | MOVIPREP, 2-Day Split-Dosing | NER1006, 2-Day Split-Dosing | NER1006,1-Day Morning Split-Dosing | Total |
|---|---|---|---|---|
| Arm/Group Description | MOVIPREP®: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 1-Day Morning Split-Dosing Regimen (to commence in the morning of the day of colonoscopy). | Total of all reporting groups |
| Overall Participants | 283 | 283 | 283 | 849 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
1
0.4%
|
0
0%
|
1
0.1%
|
| Between 18 and 65 years |
228
80.6%
|
202
71.4%
|
209
73.9%
|
639
75.3%
|
| >=65 years |
55
19.4%
|
80
28.3%
|
74
26.1%
|
209
24.6%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
54.3
(12.48)
|
56.3
(12.03)
|
54.9
(13.21)
|
55.2
(12.57)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
139
49.1%
|
163
57.6%
|
152
53.7%
|
454
53.5%
|
| Male |
144
50.9%
|
120
42.4%
|
131
46.3%
|
395
46.5%
|
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 2-Day and 1-Day versus MOVIPREP was evaluated using a non-inferiority study design. |
| Time Frame | Up to 2 days (from day of first dosing to day of 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 | MOVIPREP, 2-Day Split-Dosing | NER1006, 2-Day Split-Dosing | NER1006,1-Day Morning Split-Dosing |
|---|---|---|---|
| Arm/Group Description | MOVIPREP: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 1-Day Morning Split-Dosing Regimen (to commence in the morning of the day of colonoscopy). |
| Measure Participants | 272 | 275 | 275 |
| Successful |
238
84.1%
|
253
89.4%
|
245
86.6%
|
| Failure |
34
12%
|
22
7.8%
|
30
10.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MOVIPREP, 2-Day Split-Dosing, NER1006, 2-Day Split-Dosing |
|---|---|---|
| Comments | Hypothesis was to demonstrate non-inferiority (NI) of NER1006 2-Day to MOVIPREP (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 2-Day success rate - MOVIPREP success rate. Hochberg procedure 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 (CL) 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 favour of MOVIPREP using lower 1-sided 97.5% CL. Calculated using exact Clopper-Pearson CLs. To accommodate the comparison of 2 NER1006 regimens a hierarchical testing approach was used whereby NER1006 2-Day was assessed first and, if successful, then NER1006 1-Day was evaluated. | |
| Statistical Test of Hypothesis | p-Value | 0.055 |
| Comments | The p-value was adjusted for multiple comparisons (two 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 success rate |
| Estimated Value | 4.50 | |
| Confidence Interval |
(1-Sided) 97.5% -4.00 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MOVIPREP, 2-Day Split-Dosing, NER1006,1-Day Morning Split-Dosing |
|---|---|---|
| Comments | The hypothesis was to demonstrate NI of NER1006 1-Day to MOVIPREP (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 1-Day success rate - MOVIPREP success rate. A Hochberg procedure was used to control Type I error since there were two 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 CLs were adjusted for multiple comparisons (2 alternative primary endpoints): To be declared non-inferior, the primary endpoint must show a difference in success rates of no greater than 10% in favour of MOVIPREP using lower 1-sided 97.5% CLs. Calculated using exact Clopper-Pearson confidences limits. To accommodate the comparison of two NER1006 regimens a hierarchical testing approach will be used whereby NER1006 2-Day was assessed first and, if successful, then NER1006 1-Day was evaluated. | |
| Statistical Test of Hypothesis | p-Value | 0.328 |
| Comments | The p-value was adjusted for multiple comparisons (two 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 success rate |
| Estimated Value | 1.59 | |
| Confidence Interval |
(1-Sided) 97.5% -6.91 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 2-Day and 1-Day versus MOVIPREP was evaluated using a non-inferiority study design. |
| Time Frame | Up to 2 days (from day of first dosing to day of 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 | MOVIPREP, 2-Day Split-Dosing | NER1006, 2-Day Split-Dosing | NER1006,1-Day Morning Split-Dosing |
|---|---|---|---|
| Arm/Group Description | MOVIPREP®: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 1-Day Morning Split-Dosing Regimen (to commence in the morning of the day of colonoscopy). |
| Measure Participants | 272 | 275 | 275 |
| Excellent plus good |
41
14.5%
|
87
30.7%
|
93
32.9%
|
| Adequate plus failure |
231
81.6%
|
188
66.4%
|
182
64.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MOVIPREP, 2-Day Split-Dosing, NER1006, 2-Day Split-Dosing |
|---|---|---|
| Comments | Hypothesis was to demonstrate NI of NER1006 2-Day to MOVIPREP (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 2-Day success rate - MOVIPREP success rate. 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 | Confidence limits (CL) were adjusted for multiple comparisons (2 alternative primary endpoints): To be declared non-inferior the primary endpoint must show a difference in success rates of no greater than 10% in favour of MOVIPREP using lower 1-sided 97.5% CLs. Calculated using exact Clopper-Pearson CLs. To accommodate the comparison of two NER1006 regimens a hierarchical testing approach will be used whereby NER1006 2-Day was assessed first and, if successful, then NER1006 1-Day was evaluated. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The p-value was adjusted for multiple comparisons (two 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 | 16.56 | |
| Confidence Interval |
(1-Sided) 97.5% 8.11 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MOVIPREP, 2-Day Split-Dosing, NER1006,1-Day Morning Split-Dosing |
|---|---|---|
| Comments | Hypothesis was to demonstrate NI of NER1006 1-Day to MOVIPREP (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 1-Day success rate - MOVIPREP success rate. 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 (CLs) were adjusted for multiple comparisons (2 alternative primary endpoints): To be declared non-inferior the primary endpoint must show a difference in success rates of no greater than 10% in favour of MOVIPREP using lower 1-sided 97.5% CLs. Calculated using exact Clopper-Pearson CLs. To accommodate the comparison of 2 NER1006 regimens a hierarchical testing approach was used whereby NER1006 2-Day was assessed first and, if successful, then NER1006 1-Day was evaluated. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| 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 | 18.74 | |
| Confidence Interval |
(1-Sided) 97.5% 10.32 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 2-Day and 1-Day is used for bowel cleansing versus MOVIPREP. Adenoma detection rate (ADR) defined as the number of patients with at least one adenoma in the colon ascendens. |
| Time Frame | Up to 2 days (from day of first dosing to day of 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 | MOVIPREP, 2-Day Split-Dosing | NER1006, 2-Day Split-Dosing | NER1006,1-Day Morning Split-Dosing |
|---|---|---|---|
| Arm/Group Description | MOVIPREP®: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 1-Day Morning Split-Dosing Regimen (to commence in the morning of the day of colonoscopy). |
| Measure Participants | 272 | 275 | 275 |
| Patients with no adenomas detected |
250
88.3%
|
243
85.9%
|
243
85.9%
|
| Patients with at least one adenoma detected |
22
7.8%
|
32
11.3%
|
32
11.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MOVIPREP, 2-Day Split-Dosing, NER1006, 2-Day Split-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 2-Day rate - MOVIPREP 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 MOVIPREP using lower 1-sided 97.5% confidence limits. Calculated using exact Clopper-Pearson confidence limits. | |
| Statistical Test of Hypothesis | p-Value | 0.106 |
| Comments | To be declared superior, the key secondary endpoint must demonstrate non-inferiority and show a significant advantage for NER1006 2-Day relative to MOVIPREP 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 | 3.55 | |
| Confidence Interval |
(2-Sided) 95% -4.80 to 12.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MOVIPREP, 2-Day Split-Dosing, NER1006,1-Day Morning Split-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 1-Day rate - MOVIPREP 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 MOVIPREP using lower 1-sided 97.5% confidence limits. Calculated using exact Clopper-Pearson confidence limits. | |
| Statistical Test of Hypothesis | p-Value | 0.106 |
| Comments | To be declared superior, the key secondary endpoint must demonstrate non-inferiority and show a significant advantage for NER1006 1-Day relative to MOVIPREP 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 | 3.55 | |
| Confidence Interval |
(2-Sided) 95% -4.80 to 12.00 |
|
| 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 2-Day and 1-Day is used for bowel cleansing versus MOVIPREP. Adenoma detection rate (ADR) defined as the number of patients with at least one adenoma in the overall colon. |
| Time Frame | Up to 2 days (from day of first dosing to day of 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 | MOVIPREP, 2-Day Split-Dosing | NER1006, 2-Day Split-Dosing | NER1006,1-Day Morning Split-Dosing |
|---|---|---|---|
| Arm/Group Description | MOVIPREP: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 1-Day Morning Split-Dosing Regimen (to commence in the morning of the day of colonoscopy). |
| Measure Participants | 272 | 275 | 275 |
| Patients with no adenomas detected |
199
70.3%
|
202
71.4%
|
199
70.3%
|
| Patients with at least one adenoma detected |
73
25.8%
|
73
25.8%
|
76
26.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MOVIPREP, 2-Day Split-Dosing, NER1006, 2-Day Split-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 2-Day rate - MOVIPREP 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 MOVIPREP using lower 1-sided 97.5% confidence limits. Calculated using exact Clopper-Pearson confidence limits. | |
| Statistical Test of Hypothesis | p-Value | 0.569 |
| Comments | To be declared superior, the key secondary endpoint must demonstrate non-inferiority and show a significant advantage for NER1006 2-Day relative to MOVIPREP 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 | -0.29 | |
| Confidence Interval |
(2-Sided) 95% -8.74 to 8.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MOVIPREP, 2-Day Split-Dosing, NER1006,1-Day Morning Split-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 1-Day rate - MOVIPREP 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 MOVIPREP using lower 1-sided 97.5% confidence limits. Calculated using exact Clopper-Pearson confidence limits. | |
| Statistical Test of Hypothesis | p-Value | 0.455 |
| Comments | To be declared superior, the key secondary endpoint must demonstrate non-inferiority and show a significant advantage for NER1006 1-Day relative to MOVIPREP 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 | 0.80 | |
| Confidence Interval |
(2-Sided) 95% -7.65 to 9.11 |
|
| 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 2-Day and 1-Day is used for bowel cleansing versus MOVIPREP. Polyp detection rate (PDR) defined as the number of patients with at least one polyp in the colon ascendens. |
| Time Frame | Up to 2 days (from day of first dosing to day of 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 | MOVIPREP, 2-Day Split-Dosing | NER1006, 2-Day Split-Dosing | NER1006,1-Day Morning Split-Dosing |
|---|---|---|---|
| Arm/Group Description | MOVIPREP: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 1-Day Morning Split-Dosing Regimen (to commence in the morning of the day of colonoscopy). |
| Measure Participants | 272 | 275 | 275 |
| Patients with no polyps detected |
228
80.6%
|
211
74.6%
|
224
79.2%
|
| Patients with at least one polyp detected |
44
15.5%
|
64
22.6%
|
51
18%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MOVIPREP, 2-Day Split-Dosing, NER1006, 2-Day Split-Dosing |
|---|---|---|
| Comments | If at least one of the primary endpoints were met, then key secondary endpoints were evaluated hierarchically in a pre-specified order. Non-inferiority was concluded if the 1-sided 97.5% confidence limit difference in proportion of events between 2 groups excluded a 10% or greater difference was in favor of MOVIPREP. Formal testing was to proceed in the hierarchy if preceding key secondary endpoint had at least met non-inferiority. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | To accommodate the comparison of two NER1006 regimens, a hierarchical testing approach was used whereby NER1006 2-Day was assessed first and, if successful, then NER1006 1-Day was evaluated. Difference in Polyp Detection Rate in the colon ascendens was calculated as NER1006 2-Day rate - MOVIPREP rate (10% margin) determined using exact Clopper-Pearson confidence limits. | |
| Statistical Test of Hypothesis | p-Value | 0.024 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in PDR |
| Estimated Value | 7.10 | |
| Confidence Interval |
(2-Sided) 95% -1.41 to 15.47 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MOVIPREP, 2-Day Split-Dosing, NER1006,1-Day Morning Split-Dosing |
|---|---|---|
| Comments | If at least one of the primary endpoints were met, then key secondary endpoints were evaluated hierarchically in a pre-specified order. Non-inferiority was concluded if the 1-sided 97.5% confidence limit difference in proportion of events between 2 groups excluded a 10% or greater difference was in favor of MOVIPREP. Formal testing was to proceed in the hierarchy if preceding key secondary endpoint had at least met non-inferiority. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | To accommodate the comparison of two NER1006 regimens, a hierarchical testing approach was used whereby NER1006 2-Day was assessed first and, if successful, then NER1006 1-Day was evaluated. Difference in Polyp Detection Rate in the colon ascendens was calculated as NER1006 rate - MOVIPREP rate (10% margin) determined using exact Clopper-Pearson confidence limits. Non-inferiority of NER1006 1-Day to MOVIPREP was proven. | |
| Statistical Test of Hypothesis | p-Value | 0.268 |
| Comments | Superiority of NER1006 1-Day to MOVIPREP not demonstrated statistically. | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in PDR |
| Estimated Value | 2.37 | |
| Confidence Interval |
(2-Sided) 95% -6.12 to 10.82 |
|
| 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 number detected when MOVIPREP is used. PDR defined as the number of patients with at least one polyp in the overall colon. |
| Time Frame | Up to 2 days (from day of first dosing to day of colonoscopy) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The overall number of participants analysed is based on the mFAS. This included all randomized patients except those patients who (i) were 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 (n=822). |
| Arm/Group Title | MOVIPREP, 2-Day Split-Dosing | NER1006, 2-Day Split-Dosing | NER1006,1-Day Morning Split-Dosing |
|---|---|---|---|
| Arm/Group Description | MOVIPREP®: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 1-Day Morning Split-Dosing Regimen (to commence in the morning of the day of colonoscopy). |
| Measure Participants | 272 | 275 | 275 |
| Patients with no polyps detected |
151
53.4%
|
154
54.4%
|
151
53.4%
|
| Patients with at least one polyp detected |
121
42.8%
|
121
42.8%
|
124
43.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MOVIPREP, 2-Day Split-Dosing, NER1006, 2-Day Split-Dosing |
|---|---|---|
| Comments | If at least one of the primary endpoints were met, then key secondary endpoints were evaluated hierarchically in a pre-specified order. Non-inferiority was concluded if the 1-sided 97.5% confidence limit difference in proportion of events between 2 groups excluded a 10% or greater difference was in favor of MOVIPREP. Formal testing was to proceed in the hierarchy if preceding key secondary endpoint had at least met non-inferiority. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | To accommodate the comparison of two NER1006 regimens, a hierarchical testing approach was used whereby NER1006 2-Day was assessed first and, if successful, then NER1006 1-Day was evaluated. Difference in Polyp Detection Rate in the overall colon was calculated as NER1006 rate - MOVIPREP rate (10% margin) determined using exact Clopper-Pearson confidence intervals. | |
| Statistical Test of Hypothesis | p-Value | 0.579 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in PDR |
| Estimated Value | -0.49 | |
| Confidence Interval |
(2-Sided) 95% -8.85 to 8.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MOVIPREP, 2-Day Split-Dosing, NER1006,1-Day Morning Split-Dosing |
|---|---|---|
| Comments | If at least one of the primary endpoints were met, then key secondary endpoints were evaluated hierarchically in a pre-specified order. Non-inferiority was concluded if the 1-sided 97.5% confidence limit difference in proportion of events between 2 groups excluded a 10% or greater difference was in favor of MOVIPREP. Formal testing was to proceed in the hierarchy if preceding key secondary endpoint had at least met non-inferiority. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | To accommodate the comparison of two NER1006 regimens, a hierarchical testing approach was used whereby NER1006 2-Day was assessed first and, if successful, then NER1006 1-Day was evaluated. Difference in Polyp Detection Rate in the overall colon was calculated as NER1006 1-Day rate - MOVIPREP rate (10% margin) determined using exact Clopper-Pearson confidence limits. | |
| Statistical Test of Hypothesis | p-Value | 0.478 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in PDR |
| Estimated Value | 0.61 | |
| Confidence Interval |
(2-Sided) 95% -7.78 to 9.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Afternoon of Day 1 (first dose) to Day 9 (final clinic visit) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Treatment Emergent AEs. Safety analyses were based on the safety population, which included all randomized patients whom it could not be ruled out (from their patient diary) that they received study drug at least once (n=794). | |||||
| Arm/Group Title | MOVIPREP, 2-Day Split-Dosing | NER1006, 2-Day Split-Dosing | NER1006,1-Day Morning Split-Dosing | |||
| Arm/Group Description | MOVIPREP®: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 2-Day Split-Dosing Regimen (to commence in the evening of the day before colonoscopy). | NER1006: 1-Day Morning Split-Dosing Regimen (to commence in the morning of the day of colonoscopy). | |||
All Cause Mortality |
||||||
| MOVIPREP, 2-Day Split-Dosing | NER1006, 2-Day Split-Dosing | NER1006,1-Day Morning Split-Dosing | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| MOVIPREP, 2-Day Split-Dosing | NER1006, 2-Day Split-Dosing | NER1006,1-Day Morning Split-Dosing | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/263 (0%) | 2/262 (0.8%) | 0/269 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Procedural intestinal perforation | 0/263 (0%) | 0 | 1/262 (0.4%) | 1 | 0/269 (0%) | 0 |
| Psychiatric disorders | ||||||
| Alcohol abuse | 0/263 (0%) | 0 | 1/262 (0.4%) | 1 | 0/269 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| MOVIPREP, 2-Day Split-Dosing | NER1006, 2-Day Split-Dosing | NER1006,1-Day Morning Split-Dosing | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 31/263 (11.8%) | 41/262 (15.6%) | 49/269 (18.2%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 6/263 (2.3%) | 6 | 3/262 (1.1%) | 3 | 1/269 (0.4%) | 1 |
| Abdominal pain lower | 1/263 (0.4%) | 1 | 0/262 (0%) | 0 | 3/269 (1.1%) | 3 |
| Dry mouth | 0/263 (0%) | 0 | 3/262 (1.1%) | 3 | 3/269 (1.1%) | 3 |
| Nausea | 9/263 (3.4%) | 9 | 15/262 (5.7%) | 16 | 14/269 (5.2%) | 14 |
| Vomiting | 3/263 (1.1%) | 3 | 11/262 (4.2%) | 11 | 18/269 (6.7%) | 18 |
| General disorders | ||||||
| Fatigue | 5/263 (1.9%) | 5 | 0/262 (0%) | 0 | 0/269 (0%) | 0 |
| Feeling cold | 4/263 (1.5%) | 4 | 0/262 (0%) | 0 | 1/269 (0.4%) | 1 |
| Thirst | 2/263 (0.8%) | 2 | 2/262 (0.8%) | 2 | 5/269 (1.9%) | 5 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 1/263 (0.4%) | 1 | 1/262 (0.4%) | 1 | 4/269 (1.5%) | 4 |
| Nervous system disorders | ||||||
| Headache | 4/263 (1.5%) | 4 | 4/262 (1.5%) | 4 | 2/269 (0.7%) | 3 |
| Vascular disorders | ||||||
| Hypertension | 0/263 (0%) | 0 | 2/262 (0.8%) | 2 | 3/269 (1.1%) | 3 |
Limitations/Caveats
Imputation of failure occurred in 4% of patients. This strict analytical approach reduced the cleansing success rates for both treatments.
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 |
Responsible Party:
Norgine
ClinicalTrials.gov Identifier:
NCT02273167
Other Study ID Numbers:
- NER1006-02/2014 (MORA)
First Posted:
Oct 23, 2014
Last Update Posted:
May 15, 2018
Last Verified:
Apr 1, 2018