Bowel Cleansing
Conditions
Keywords
preparation
Brief summary
The purpose of this study is to demonstrate that Eziclen is non-inferior to Fortrans® (the reference colonic lavage in Russia) administered in adult subjects scheduled to undergo colonoscopy for a routinely accepted diagnostic indication.
Interventions
DRUGEziclen
Eziclen solution administered orally as split-dose the day before and on the day of colonoscopy.
DRUGFortrans®
Fortrans® solution administered orally as split-dose the day before and on the day of colonoscopy.
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent signed prior to any study related procedures * Male or female, at least 18 years old undergoing colonoscopy for a routine diagnostic indication: 1. Routine cancer screening 2. Polyp or neoplasm history 3. Diagnostic procedure for occult bleeding or anaemia 4. Diarrhoea or constipation of unknown aetiology 5. IBD if not in severe acute phase 6. Abnormal ultrasound exam (i.e. mass in abdomen) 7. Evaluation of barium enema or computed tomography (CT) scan results * In good clinical condition (physical exam and medical history) * Subjects with an adequate fluid balance, and adequate electrolyte balance (measured during screening K, Na, Cl, bicarbonate within normal/near normal range)
Exclusion criteria
* Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardise the subject's safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study. * Has an advanced carcinoma or any other colon disease leading to excessive mucosal fragility. * Has a known or suspected gastrointestinal (GI) obstruction, gastric retention, gastroparesis, or disorder of gastric emptying. * Has a known or suspected ileus. * Has a bowel perforation. * Has profuse vomiting. * Needs a therapeutic procedure (e.g. polypectomy, mucosectomy). * Has toxic colitis or megacolon. * Is in severe acute phases of active IBD, as a contraindication for colonoscopy. * Has acute GI bleeding. * Underwent previous GI surgeries (e.g. colostomy, colectomy, gastric bypass, stomach stapling). * Has impaired consciousness predisposing to pulmonary aspiration. * Needs a colonoscopy for foreign body removal and decompression. * Underwent previous incomplete colonoscopy. * Has a known severe renal insufficiency (glomerular filtration rate (GFR) \<30 mL/min/1.73 m2). * Has a known severe liver insufficiency (Child-Pugh grade C: 10 to 15 points). * Suffers from uncorrected dehydration. * Has ascites. * Suffers from severe congestive heart failure (classes III and IV). * Has hyperuricemia with clinical manifestation as gouty arthritis. * Is pregnant or lactating. * Is a female at risk of pregnancy and not using an acceptable contraceptive method during the study. Females of childbearing potential must provide a negative pregnancy test at start of study and must be using oral, double barrier (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide), or injectable contraception or an intra-uterine device. Nonchildbearing potential is defined as postmenopause for at least one year, surgical sterilisation or hysterectomy at least three months before the start of the study. * Has any known hypersensitivity to the active substances or to any of the preparation excipients (Eziclen or Fortrans®: polyethylene glycol (PEG) (macrogol), sodium sulphate, potassium sulphate, magnesium sulphate, sodium chloride, potassium chloride, sodium bicarbonate, sucralose, sodium saccharin, sodium benzoate, citric acid, malic acid, and fruit cocktail flavor). * Patient has any mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude * Patient was treated with any other IMP within the last 30 days before study entry * Patient is likely to require treatment during the study with drugs that are not permitted by the study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Percentage of Patients With Successful Overall Colon Preparation, Assessed by the Global Score of the Boston Bowel Preparation Scale (BBPS). | Colonoscopy was performed on Day 2. | The BBPS score for each colon segment (right, transverse and left colon) was assessed by 3 blinded experts as follows: 0=unprepared segment with mucosa not seen due to solid stool that cannot be cleared , 1=portion of mucosa of the segment seen, but other areas not well seen due to staining, residual stool and/or opaque liquid, 2=-minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of segment seen well, 3=entire mucosa of segment seen well with no residual staining, small fragments of stool and/or opaque liquid. A reconciled score based on the 3 blinded reviews was used to calculate the global BBPS score, ranging from 0 to 9 (worst to best). A successful overall colon preparation was defined as a global score ≥6 for the 3 colon segments. The percentage of patients with a successful preparation was determined using a logistic regression model, adjusted on centre, age class (\<= 65; \> 65), gender and inflammatory bowel disease (IBD) status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean BBPS Score for Right Colon and Transverse Colon Segment (PP Population) | Colonoscopy was performed on Day 2. | The mean colon segment BBPS scores for the Right Colon and Transverse Colon segments for the PP population are presented. For each of the colon segments (right and transverse colon) the BBPS score ranges from 0 - 3 (worst to best), and was assessed by 3 blinded experts as follows: * unprepared colon segment with mucosa not seen due to solid stool that cannot be cleared = 0 * portion of mucosa of the colon segment seen, but other areas of the colon segment not well seen due to staining, residual stool and/or opaque liquid = 1 * minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of colon segment seen well = 2 * entire mucosa of colon segment seen well with no residual staining, small fragments of stool and/or opaque liquid = 3. Reconciled scores were based on the 3 blinded reviews. |
| The Percentage of Patients in Whom Lesions Were Detected. | Colonoscopy was performed on Day 2. | The percentage of patients for whom polyps, adenomas and other lesions were detected during the colonoscopy are presented. |
| The Percentage of Patients for Whom the Colonoscopy Was Completed | Colonoscopy was performed on Day 2. | The percentage of patients for whom a total colonoscopy could be completed is presented. |
| Mean BBPS Score by Segment and Globally (ITT Population) | Colonoscopy was performed on Day 2. | The mean global BBPS scores and scores by colon segment are presented for the ITT population. For each of the 3 colon segments (right, transverse and left colon) the BBPS score ranges from 0 - 3 (worst to best), and was assessed by 3 blinded experts: * unprepared colon segment with mucosa not seen due to solid stool that cannot be cleared = 0 * portion of mucosa of the colon segment seen, but other areas of the colon segment not well seen due to staining, residual stool and/or opaque liquid = 1 * minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of colon segment seen well = 2 * entire mucosa of colon segment seen well with no residual staining, small fragments of stool and/or opaque liquid = 3. The global score is the total of the 3 segment scores ranging from 0 - 9 (worst to best). Reconciled scores were based on 3 blinded reviews. Results of analysis for the PP population for right + transverse colon segments presented separately. |
| Investigator Satisfaction as Determined by Mean Likert Scale Score for Global Evaluation | Colonoscopy was performed on Day 2. | Investigator satisfaction with the procedure was measured by the mean Likert scale score for global evaluation by the investigator. The Likert scale consists of 5 points, and ranges from 0 (poor cleansing) to 4 (excellent cleansing) as follows: * presence of faeces and soiled fluid: investigation could not be reliably performed = 0 * presence of faecal material and of unclear fluid, with negative effect on the reliability of the investigation = 1 * brown liquid, no solid faecal material, presence of unclear residual fluid that could be aspirated: no effect on the reliability of the investigation = 2 * absence of solid faecal material, presence of clear residual fluid = 3 * no faecal material, no residual fluid, empty colon = 4. |
| Evaluation of Patient Compliance as Determined by the Percentage of Patients Who Consumed All the Planned Volume of Study Treatment | Study treatment was administered as a split-dose on Days 1 and 2. | Patient compliance was evaluated based on the percentage of patients who consumed all the planned volume of the study treatment. A patient was considered compliant with the instructions of use provided in the prescription if he/she drank the whole preparation and any required further fluid intake. The percentage of compliant patients is presented. |
| Mean Colonoscopy Duration | Colonoscopy was performed on Day 2. | The mean colonoscopy duration per treatment group is presented. The duration of colonoscopy was defined as the time from colonoscopy insertion to the time to reach the caecum in minutes. |
Countries
Russia
Participant flow
Recruitment details
Adult patients due to undergo colonoscopy for a routine diagnostic indication were enrolled into this noninferiority phase 3 study at 3 study centres in Russia. First patient started: 13 March 2015; last patient completed: 28 December 2015.
Pre-assignment details
305 patients were screened for inclusion, and 296 patients met all inclusion criteria and none of the exclusion criteria and were randomised to treatment. 294 patients received study treatment, and 2 patients were excluded from the safety and intention-to-treat (ITT) populations as they did not receive study treatment prior to colonoscopy.
Participants by arm
| Arm | Count |
|---|---|
| Eziclen Patients were randomised to receive an oral split-dose of Eziclen on Day 1 and Day 2. The first dose was taken the evening of Day 1 before the colonoscopy and the second dose was taken 10 - 12 hours after the evening dose on the day of the colonoscopy. Colonoscopy was performed on Day 2, at least 1 hour and no more than 6 hours after the last dose of Eziclen. | 147 |
| Fortrans® Patients were randomised to receive an oral split-dose of Fortrans® on Day 1 and Day 2. The first dose was taken the evening of Day 1 before the colonoscopy and the second dose was taken 10 - 12 hours after the evening dose on the day of the colonoscopy. Colonoscopy was performed on Day 2, at least 3 hours and no more than 6 hours after the last dose of Fortrans®. | 147 |
| Total Title | 294 |
| Total | 588 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Subject withdrawn before any treatment | 1 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | Eziclen | Fortrans® | Total Title |
|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 13 | 54.0 years STANDARD_DEVIATION 13 | 53.8 years STANDARD_DEVIATION 12.9 |
| Sex: Female, Male Female | 108 Participants | 105 Participants | 213 Participants |
| Sex: Female, Male Male | 39 Participants | 42 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 147 | 0 / 147 |
| other Total, other adverse events | 101 / 147 | 81 / 147 |
| serious Total, serious adverse events | 1 / 147 | 0 / 147 |
Outcome results
Primary
Adjusted Percentage of Patients With Successful Overall Colon Preparation, Assessed by the Global Score of the Boston Bowel Preparation Scale (BBPS).
The BBPS score for each colon segment (right, transverse and left colon) was assessed by 3 blinded experts as follows: 0=unprepared segment with mucosa not seen due to solid stool that cannot be cleared , 1=portion of mucosa of the segment seen, but other areas not well seen due to staining, residual stool and/or opaque liquid, 2=-minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of segment seen well, 3=entire mucosa of segment seen well with no residual staining, small fragments of stool and/or opaque liquid. A reconciled score based on the 3 blinded reviews was used to calculate the global BBPS score, ranging from 0 to 9 (worst to best). A successful overall colon preparation was defined as a global score ≥6 for the 3 colon segments. The percentage of patients with a successful preparation was determined using a logistic regression model, adjusted on centre, age class (\<= 65; \> 65), gender and inflammatory bowel disease (IBD) status.
Time frame: Colonoscopy was performed on Day 2.
Population: The per protocol (PP) population consisted of all randomised patients who received the preparation of study treatment (complete or partial), who underwent the colonoscopy procedure and for whom no major protocol violation occurred until colonoscopy. Patients were assessed according to the randomised treatment, regardless of treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eziclen | Adjusted Percentage of Patients With Successful Overall Colon Preparation, Assessed by the Global Score of the Boston Bowel Preparation Scale (BBPS). | 97.18 Adjusted percentage of patients |
| Fortrans® | Adjusted Percentage of Patients With Successful Overall Colon Preparation, Assessed by the Global Score of the Boston Bowel Preparation Scale (BBPS). | 97.65 Adjusted percentage of patients |
Comparison: A multivariate logistic regression model, adjusted on centre, age class (≤65; \>65), gender and IBD status (No IBD, IBD) was used.95% CI: [-4.22, 3.29]
Secondary
Evaluation of Patient Compliance as Determined by the Percentage of Patients Who Consumed All the Planned Volume of Study Treatment
Patient compliance was evaluated based on the percentage of patients who consumed all the planned volume of the study treatment. A patient was considered compliant with the instructions of use provided in the prescription if he/she drank the whole preparation and any required further fluid intake. The percentage of compliant patients is presented.
Time frame: Study treatment was administered as a split-dose on Days 1 and 2.
Population: The ITT population consisted of all randomised patients who received even a partial dose of study treatment. Patients were assessed according to the randomised treatment, regardless of treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eziclen | Evaluation of Patient Compliance as Determined by the Percentage of Patients Who Consumed All the Planned Volume of Study Treatment | 96.6 percentage of participants |
| Fortrans® | Evaluation of Patient Compliance as Determined by the Percentage of Patients Who Consumed All the Planned Volume of Study Treatment | 84.5 percentage of participants |
p-value: =0.001195% CI: [6.37, 20.32]Regression, Logistic
Secondary
Investigator Satisfaction as Determined by Mean Likert Scale Score for Global Evaluation
Investigator satisfaction with the procedure was measured by the mean Likert scale score for global evaluation by the investigator. The Likert scale consists of 5 points, and ranges from 0 (poor cleansing) to 4 (excellent cleansing) as follows: * presence of faeces and soiled fluid: investigation could not be reliably performed = 0 * presence of faecal material and of unclear fluid, with negative effect on the reliability of the investigation = 1 * brown liquid, no solid faecal material, presence of unclear residual fluid that could be aspirated: no effect on the reliability of the investigation = 2 * absence of solid faecal material, presence of clear residual fluid = 3 * no faecal material, no residual fluid, empty colon = 4.
Time frame: Colonoscopy was performed on Day 2.
Population: The ITT population consisted of all randomised patients who received even a partial dose of study treatment. Patients were assessed according to the randomised treatment, regardless of treatment received. Only patients with data available are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eziclen | Investigator Satisfaction as Determined by Mean Likert Scale Score for Global Evaluation | 3.03 units on a scale | Standard Deviation 0.61 |
| Fortrans® | Investigator Satisfaction as Determined by Mean Likert Scale Score for Global Evaluation | 2.93 units on a scale | Standard Deviation 0.72 |
p-value: =0.189195% CI: [-0.05, 0.25]ANOVA
Secondary
Mean BBPS Score by Segment and Globally (ITT Population)
The mean global BBPS scores and scores by colon segment are presented for the ITT population. For each of the 3 colon segments (right, transverse and left colon) the BBPS score ranges from 0 - 3 (worst to best), and was assessed by 3 blinded experts: * unprepared colon segment with mucosa not seen due to solid stool that cannot be cleared = 0 * portion of mucosa of the colon segment seen, but other areas of the colon segment not well seen due to staining, residual stool and/or opaque liquid = 1 * minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of colon segment seen well = 2 * entire mucosa of colon segment seen well with no residual staining, small fragments of stool and/or opaque liquid = 3. The global score is the total of the 3 segment scores ranging from 0 - 9 (worst to best). Reconciled scores were based on 3 blinded reviews. Results of analysis for the PP population for right + transverse colon segments presented separately.
Time frame: Colonoscopy was performed on Day 2.
Population: The ITT population consisted of all randomised patients who received even a partial dose of study treatment. Patients were assessed according to the randomised treatment, regardless of treatment received. Only patients with data available are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eziclen | Mean BBPS Score by Segment and Globally (ITT Population) | Right Colon BBPS Score | 2.56 units on a scale | Standard Deviation 0.58 |
| Eziclen | Mean BBPS Score by Segment and Globally (ITT Population) | Transverse Colon BBPS Score | 2.78 units on a scale | Standard Deviation 0.43 |
| Eziclen | Mean BBPS Score by Segment and Globally (ITT Population) | Left Colon BBPS Score | 2.84 units on a scale | Standard Deviation 0.39 |
| Eziclen | Mean BBPS Score by Segment and Globally (ITT Population) | Global BBPS Score | 8.17 units on a scale | Standard Deviation 1.21 |
| Fortrans® | Mean BBPS Score by Segment and Globally (ITT Population) | Global BBPS Score | 7.86 units on a scale | Standard Deviation 1.39 |
| Fortrans® | Mean BBPS Score by Segment and Globally (ITT Population) | Right Colon BBPS Score | 2.42 units on a scale | Standard Deviation 0.62 |
| Fortrans® | Mean BBPS Score by Segment and Globally (ITT Population) | Left Colon BBPS Score | 2.78 units on a scale | Standard Deviation 0.48 |
| Fortrans® | Mean BBPS Score by Segment and Globally (ITT Population) | Transverse Colon BBPS Score | 2.67 units on a scale | Standard Deviation 0.52 |
Comparison: Treatment difference for Right Colon BBPS Score.p-value: =0.024995% CI: [0.02, 0.28]ANOVA
Comparison: Treatment difference for Transverse Colon BBPS Score.p-value: =0.038295% CI: [0.01, 0.22]ANOVA
Comparison: Treatment difference for Left Colon BBPS Score.p-value: =0.253895% CI: [-0.04, 0.16]ANOVA
Comparison: Treatment difference for Global BBPS Score.p-value: =0.025695% CI: [0.04, 0.62]ANOVA
Secondary
Mean BBPS Score for Right Colon and Transverse Colon Segment (PP Population)
The mean colon segment BBPS scores for the Right Colon and Transverse Colon segments for the PP population are presented. For each of the colon segments (right and transverse colon) the BBPS score ranges from 0 - 3 (worst to best), and was assessed by 3 blinded experts as follows: * unprepared colon segment with mucosa not seen due to solid stool that cannot be cleared = 0 * portion of mucosa of the colon segment seen, but other areas of the colon segment not well seen due to staining, residual stool and/or opaque liquid = 1 * minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of colon segment seen well = 2 * entire mucosa of colon segment seen well with no residual staining, small fragments of stool and/or opaque liquid = 3. Reconciled scores were based on the 3 blinded reviews.
Time frame: Colonoscopy was performed on Day 2.
Population: The PP population consisted of all randomised patients who received the preparation of study treatment (whether complete or partial), who underwent the colonoscopy procedure and for whom no protocol violation occurred until colonoscopy. Patients were assessed according to the randomised treatment, regardless of treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eziclen | Mean BBPS Score for Right Colon and Transverse Colon Segment (PP Population) | Right Colon BBPS Score | 2.55 units on a scale | Standard Deviation 0.58 |
| Eziclen | Mean BBPS Score for Right Colon and Transverse Colon Segment (PP Population) | Transverse Colon BBPS Score | 2.78 units on a scale | Standard Deviation 0.43 |
| Fortrans® | Mean BBPS Score for Right Colon and Transverse Colon Segment (PP Population) | Right Colon BBPS Score | 2.46 units on a scale | Standard Deviation 0.56 |
| Fortrans® | Mean BBPS Score for Right Colon and Transverse Colon Segment (PP Population) | Transverse Colon BBPS Score | 2.70 units on a scale | Standard Deviation 0.46 |
Comparison: Treatment difference for Right Colon BBPS Score (per protocol population).p-value: =0.08495% CI: [-0.02, 0.24]ANOVA
Comparison: Treatment difference for Transverse Colon BBPS Score (per protocol population).p-value: =0.13295% CI: [-0.02, 0.18]ANOVA
Secondary
Mean Colonoscopy Duration
The mean colonoscopy duration per treatment group is presented. The duration of colonoscopy was defined as the time from colonoscopy insertion to the time to reach the caecum in minutes.
Time frame: Colonoscopy was performed on Day 2.
Population: The ITT population consisted of all randomised patients who received even a partial dose of study treatment. Patients were assessed according to the randomised treatment, regardless of treatment received. Only patients with data available are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eziclen | Mean Colonoscopy Duration | 9.80 minutes | Standard Deviation 6.93 |
| Fortrans® | Mean Colonoscopy Duration | 10.03 minutes | Standard Deviation 6.87 |
p-value: =0.703995% CI: [-1.88, 1.27]ANOVA
Secondary
The Percentage of Patients for Whom the Colonoscopy Was Completed
The percentage of patients for whom a total colonoscopy could be completed is presented.
Time frame: Colonoscopy was performed on Day 2.
Population: The ITT population consisted of all randomised patients who received even a partial dose of study treatment. Patients were assessed according to the randomised treatment, regardless of treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eziclen | The Percentage of Patients for Whom the Colonoscopy Was Completed | 96.6 percentage of participants |
| Fortrans® | The Percentage of Patients for Whom the Colonoscopy Was Completed | 97.3 percentage of participants |
p-value: =0.992795% CI: [-3.12, 3.14]Regression, Logistic
Secondary
The Percentage of Patients in Whom Lesions Were Detected.
The percentage of patients for whom polyps, adenomas and other lesions were detected during the colonoscopy are presented.
Time frame: Colonoscopy was performed on Day 2.
Population: The ITT population consisted of all randomised patients who received even a partial dose of study treatment. Patients were assessed according to the randomised treatment, regardless of treatment received. Percentages are calculated based on the overall ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eziclen | The Percentage of Patients in Whom Lesions Were Detected. | Polyps detected | 27.4 percentage of participants |
| Eziclen | The Percentage of Patients in Whom Lesions Were Detected. | Adenomas detected | 20.5 percentage of participants |
| Eziclen | The Percentage of Patients in Whom Lesions Were Detected. | Other lesions detected | 15.1 percentage of participants |
| Fortrans® | The Percentage of Patients in Whom Lesions Were Detected. | Polyps detected | 33.8 percentage of participants |
| Fortrans® | The Percentage of Patients in Whom Lesions Were Detected. | Adenomas detected | 18.9 percentage of participants |
| Fortrans® | The Percentage of Patients in Whom Lesions Were Detected. | Other lesions detected | 16.9 percentage of participants |
Comparison: Treatment difference for detection of polyps.p-value: =0.219995% CI: [-17.53, 3.64]Regression, Logistic
Comparison: Treatment difference for detection of adenomas.p-value: =0.632595% CI: [-6.25, 9.99]Regression, Logistic
Comparison: Treatment difference for detection of other lesions.p-value: =0.708695% CI: [-9.64, 6.54]Regression, Logistic