Multicenter Randomized Parallel Group Phase III Study Com... | NCT02273141

NCT02273141

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
NER1006, Day Before-Only Dosing	Experimental	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
SP+MS, Day Before-Only Dosing	Active Comparator	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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
NER1006, Day Before-Only Dosing	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Patients With Successful Bowel Cleansing (Overall Colon)	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.	One day (day before colonoscopy)
Number of Patients With 'Excellent Plus Good' (Highly Effective) Bowel Cleansing (Colon Ascendens)	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.	One day (day before colonoscopy)

Secondary Outcomes

Measure	Description	Time Frame
Adenoma Detection Rate (Colon Ascendens)	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.	One day (day before colonoscopy).

Eligibility Module

Eligibility 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/Locations Module

Name	Affiliation	Role
Stefan Schreiber	University Hospital Schleswig-Holstein	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Charité - Campus Virchow Klinikum		Berlin			Germany
University Hospital Schleswig-Holstein

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36064325	Derived	Cash BD, Allen C, Poppers DM. Transient alterations in plasma sodium concentrations with NER1006 bowel preparation: an analysis of three phase III, randomized clinical trials. BMC Gastroenterol. 2022 Sep 5;22(1):412. doi: 10.1186/s12876-022-02484-7.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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).
FG001	NER1006, Day Before-Only Dosing

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

NER1006, Day Before-Only Dosing

NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).

The number of participants for analysis, 220 per arm, was based on assumed overall cleansing success rates of 70% for SP+MS and 75% for NER1006, a non-inferiority margin of 10%, and at least 90% power to demonstrate non-inferiority. The overall number of participants analyzed was based on the modified full analysis set (mFAS).

Arm/Group Information

ID	Title	Description
BG000	SP+MS, Day Before-Only Dosing	SP+MS 1-Day Day Before-Only Split-Dosing Regimen (to commence on the moring of the day before colonoscopy).
BG001	NER1006, Day Before-Only Dosing	NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000257 BG001258 BG002515

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0011 BG0021
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00052.9± 13.35 BG00154.6± 11.64 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000174 BG001168 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Patients With Successful Bowel Cleansing (Overall Colon)

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.

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.

Posted

Count of Participants

Participants

One day (day before colonoscopy)

ID	Title	Description
OG000	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).
OG001	NER1006, Day Before-Only Dosing	NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).

Units	Counts
Participants	OG000251 OG001250

Title

Denominators

Categories

Successful

Title	Measurements
	OG000135 OG001155

Failure

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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.	Fisher Exact		0.038	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.	Difference in success rate	8.22			1-Sided	97.5	-0.50

Primary

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

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.

Posted

Count of Participants

Participants

One day (day before colonoscopy)

ID	Title	Description
OG000	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).
OG001	NER1006, Day Before-Only Dosing	NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).

Secondary

Adenoma Detection Rate (Colon Ascendens)

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.

Posted

Count of Participants

Participants

One day (day before colonoscopy).

ID	Title	Description
OG000	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).
OG001	NER1006, Day Before-Only Dosing	NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).

Units	Counts
Participants

Secondary

Adenoma Detection Rate (Overall Colon)

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.

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).

Posted

Count of Participants

Participants

One day (day before colonoscopy)

ID	Title	Description
OG000	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).
OG001	NER1006, Day Before-Only Dosing	NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).

Units	Counts
Participants

Secondary

Polyp Detection Rate (Colon Ascendens)

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.

Posted

Count of Participants

Participants

One day (day before colonoscopy)

ID	Title	Description
OG000	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).
OG001	NER1006, Day Before-Only Dosing	NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).

Units	Counts
Participants

Secondary

Polyp Detection Rate (Overall Colon)

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.

Posted

Count of Participants

Participants

One day (day before colonoscopy)

ID	Title	Description
OG000	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).
OG001	NER1006, Day Before-Only Dosing	NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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).	0	241	0	241	9	241
EG001	NER1006, Day Before-Only Dosing	NER1006 1-Day Day Before-Only Split-Dosing Regimen (to commence on the evening of the day before colonoscopy).	0	235	1	235	32	235

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Ovarian abscess	Infections and infestations	MedDRA 18.0	Non-systematic Assessment		EG0000 events0 affected241 at risk EG0011 events1 affected235 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events3 affected241 at risk EG0018 events8 affected235 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected241 at risk EG0016 events6 affected235 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected241 at risk EG00111 events11 affected235 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected241 at risk EG0013 events3 affected235 at risk
Headache	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0004 events4 affected241 at risk EG0015 events4 affected235 at risk

Imputation of failure occurred in 4% of patients. This strict analytical approach reduced the cleansing success rates for both treatments.

Certain Agreements

ID	Term
D015179	Colorectal Neoplasms

Ancestor Terms

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases

Units	Counts
Participants	OG000251 OG001250