Bowel Cleansing
Conditions
Brief summary
This was a phase 3, randomised, assessor-blinded, multi-centre trial comparing the efficacy, safety and tolerability of a PICOPREP tailored dosing schedule to the PICOPREP day-before dosing schedule for colon cleansing in preparation for colonoscopy.
Interventions
DRUGPICOPREP
Sodium Picosulfate, Magnesium Oxide and Citric Acid as PICOPREP powder for oral solution
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, 18 years of age or above, being scheduled to undergo elective colonoscopy * Subjects must have had more than or equal to 3 spontaneous bowel movements (i.e. without use of any laxative within 24 hours before the bowel movement, with the exception for bulk-forming laxatives (ATC code A06AC)) per week for one month prior to the colonoscopy
Exclusion criteria
* Acute surgical abdominal conditions (e.g. acute obstruction or perforation, etc.) * Active (acute/exacerbation of/severe/uncontrolled) Inflammatory Bowel Disease (IBD) * Any prior colorectal surgery, excluding appendectomy, haemorrhoid surgery or prior endoscopic procedures * Colon disease (history of colonic cancer, toxic megacolon, toxic colitis, idiopathic pseudoobstruction, hypomotility syndrome) * Ascites * Gastrointestinal disorder (active ulcer, outlet obstruction, retention, gastroparesis, ileus) * Upper gastrointestinal surgery (gastric resection, gastric banding, gastric by-pass) * Severely reduced renal function (Glomerular filtration rate (GFR) \<30 (mL/min/1.73 m2)) * The subject is a pregnant (positive urine pregnancy test at Visit 1 or Visit 2) woman. Women of childbearing potential (defined, for the purpose of this trial, as all females post-puberty, not postmenopausal ≥2 years, or not surgically sterile) who do not agree to use one of the following methods of birth control from the day of signing the Informed Consent Form until End of Trial Visit are excluded: 1. Transdermal patch 2. Hormonal contraception (i.e., oral, implant, or injectable contraceptive) 3. Double-barrier birth control (i.e., condom plus intrauterine device, diaphragm plus spermicide, etc.) 4. Maintenance of a monogamous relationship with a male who has been surgically sterilised by vasectomy 5. Sexual abstinence * The subject is a breast-feeding or lactating woman
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Colon Cleansing Procedure (ITT) Measured by the Total Ottawa Scale | Day 1 (day of colonoscopy) | Measured by the total Ottawa Scale score during the colonoscopy performed by a colonoscopist blinded to the dosing schedules. Total Ottawa Scale score was computed by adding the ratings (0 to 4; 0=excellent, 1=good, 2=fair, 3=poor, 4=inadequate) for each of the three colon segments and the overall fluid quality rating (0 to 2). The final score ranged from 0 (excellent) to 14 (solid stool in each colon segment and lots of fluid). |
| Overall Colon Cleansing Procedure (PP) Measured by the Total Ottawa Scale | Day 1 (day of colonoscopy) | Measured by the total Ottawa Scale score during the colonoscopy which is performed by a colonoscopist blinded to the dosing schedules. Total Ottawa Scale score was computed by adding the ratings (0 to 4; 0=excellent, 1=good, 2=fair, 3=poor, 4=inadequate) for each of the three colon segments and the overall fluid quality rating (0 to 2). The final score ranged from 0 (excellent) to 14 (solid stool in each colon segment and lots of fluid). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ascending Colon Cleansing Responder Status (ITT) | Day 1 (day of colonoscopy) | Percentage of subjects classified as responders, i.e. Ottawa Scale score of either 0 (excellent) or 1 (good), during colonoscopy performed by a colonoscopist blinded to the dosing schedules. |
| Frequency and Intensity of Adverse Events | From baseline (screening) up to day 10 after colonoscopy | — |
| Clinically Significant Changes in Vital Signs (Pulse and Blood Pressure) | From baseline (screening) up to day 10 after colonoscopy (inclusive of assessment at each visit) | Mean change from baseline to the end-of-trial was observed for pulse and blood pressure (systolic and diastolic). |
| Clinically Significant Changes in Laboratory Values (Haematology, Clinical Chemistry, Coagulation and Urinalysis) | From baseline (screening) up to day 10 after colonoscopy (inclusive of assessment at each visit) | Laboratory parameters included routine haematology, clinical chemistry, coagulation and urinalysis. With the exception of urinalysis and urine pregnancy test, which was performed as dip-stick analyses at the trial site, all laboratory tests were analysed by a central laboratory. |
Countries
France, Germany, Netherlands
Participant flow
Recruitment details
Subjects were recruited from 11 sites in Germany, France and the Netherlands from Nov 2014 to Jun 2015.
Participants by arm
| Arm | Count |
|---|---|
| PICOPREP Day-before Dosing Schedule Dose 1 was given before 8:00 AM on day before colonoscopy and Dose 2 was given 6-8 hours after Dose 1.
PICOPREP: Sodium Picosulfate, Magnesium Oxide and Citric Acid as PICOPREP powder for oral solution | 73 |
| PICOPREP Tailored Dosing Schedule Dose 1 was given 10-18 hours before colonoscopy and Dose 2 was given 4-6 hours before colonoscopy.
PICOPREP: Sodium Picosulfate, Magnesium Oxide and Citric Acid as PICOPREP powder for oral solution | 131 |
| Total | 204 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Incomplete colonoscopy | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Other reason | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | PICOPREP Day-before Dosing Schedule | PICOPREP Tailored Dosing Schedule | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 24 Participants | 46 Participants | 70 Participants |
| Age, Categorical Between 18 and 65 years | 49 Participants | 85 Participants | 134 Participants |
| Age, Continuous | 56.6 years STANDARD_DEVIATION 15.1 | 58.4 years STANDARD_DEVIATION 13.3 | 57.8 years STANDARD_DEVIATION 13.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants | 128 Participants | 199 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 73 Participants | 130 Participants | 203 Participants |
| Sex: Female, Male Female | 43 Participants | 77 Participants | 120 Participants |
| Sex: Female, Male Male | 30 Participants | 54 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 70 | 14 / 125 |
| serious Total, serious adverse events | 0 / 70 | 1 / 125 |
Outcome results
Primary
Overall Colon Cleansing Procedure (ITT) Measured by the Total Ottawa Scale
Measured by the total Ottawa Scale score during the colonoscopy performed by a colonoscopist blinded to the dosing schedules. Total Ottawa Scale score was computed by adding the ratings (0 to 4; 0=excellent, 1=good, 2=fair, 3=poor, 4=inadequate) for each of the three colon segments and the overall fluid quality rating (0 to 2). The final score ranged from 0 (excellent) to 14 (solid stool in each colon segment and lots of fluid).
Time frame: Day 1 (day of colonoscopy)
Population: The ITT analysis set consisted of all randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PICOPREP Day-before Dosing Schedule | Overall Colon Cleansing Procedure (ITT) Measured by the Total Ottawa Scale | 8.2 score on a scale | Standard Deviation 3.54 |
| PICOPREP Tailored Dosing Schedule | Overall Colon Cleansing Procedure (ITT) Measured by the Total Ottawa Scale | 4.2 score on a scale | Standard Deviation 3.75 |
Comparison: Null hypothesis was no treatment difference between the two dosing schedules.p-value: <0.000195% CI: [-4.99, -2.87]ANCOVA
Primary
Overall Colon Cleansing Procedure (PP) Measured by the Total Ottawa Scale
Measured by the total Ottawa Scale score during the colonoscopy which is performed by a colonoscopist blinded to the dosing schedules. Total Ottawa Scale score was computed by adding the ratings (0 to 4; 0=excellent, 1=good, 2=fair, 3=poor, 4=inadequate) for each of the three colon segments and the overall fluid quality rating (0 to 2). The final score ranged from 0 (excellent) to 14 (solid stool in each colon segment and lots of fluid).
Time frame: Day 1 (day of colonoscopy)
Population: The per-protocol (PP) analysis set consisted of all the subjects included in ITT analysis set, but excluding subjects with major protocol deviations (18 subjects) that would impact efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PICOPREP Day-before Dosing Schedule | Overall Colon Cleansing Procedure (PP) Measured by the Total Ottawa Scale | 8.1 score on a scale | Standard Deviation 3.38 |
| PICOPREP Tailored Dosing Schedule | Overall Colon Cleansing Procedure (PP) Measured by the Total Ottawa Scale | 3.7 score on a scale | Standard Deviation 3.14 |
Comparison: Null hypothesis was no treatment difference between the two dosing schedules.p-value: <0.000195% CI: [-5.34, -3.41]ANCOVA
Secondary
Ascending Colon Cleansing Responder Status (ITT)
Percentage of subjects classified as responders, i.e. Ottawa Scale score of either 0 (excellent) or 1 (good), during colonoscopy performed by a colonoscopist blinded to the dosing schedules.
Time frame: Day 1 (day of colonoscopy)
Population: The ITT analysis set consisted of all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PICOPREP Day-before Dosing Schedule | Ascending Colon Cleansing Responder Status (ITT) | 15.1 percentage of subjects |
| PICOPREP Tailored Dosing Schedule | Ascending Colon Cleansing Responder Status (ITT) | 61.1 percentage of subjects |
Comparison: Null hypothesis was no treatment difference between the two dosing schedules.p-value: <0.000195% CI: [4.36, 19.32]Regression, Logistic
Secondary
Clinically Significant Changes in Laboratory Values (Haematology, Clinical Chemistry, Coagulation and Urinalysis)
Laboratory parameters included routine haematology, clinical chemistry, coagulation and urinalysis. With the exception of urinalysis and urine pregnancy test, which was performed as dip-stick analyses at the trial site, all laboratory tests were analysed by a central laboratory.
Time frame: From baseline (screening) up to day 10 after colonoscopy (inclusive of assessment at each visit)
Population: The Safety analysis set consisted of all treated subjects and was analyzed according to the actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PICOPREP Day-before Dosing Schedule | Clinically Significant Changes in Laboratory Values (Haematology, Clinical Chemistry, Coagulation and Urinalysis) | Clinically significant change in urinalysis | 0 subjects |
| PICOPREP Day-before Dosing Schedule | Clinically Significant Changes in Laboratory Values (Haematology, Clinical Chemistry, Coagulation and Urinalysis) | Clinically significant change in clinical chem | 0 subjects |
| PICOPREP Day-before Dosing Schedule | Clinically Significant Changes in Laboratory Values (Haematology, Clinical Chemistry, Coagulation and Urinalysis) | Clinically significant change in haematology | 0 subjects |
| PICOPREP Day-before Dosing Schedule | Clinically Significant Changes in Laboratory Values (Haematology, Clinical Chemistry, Coagulation and Urinalysis) | Clinically significant change in coagulation | 0 subjects |
| PICOPREP Tailored Dosing Schedule | Clinically Significant Changes in Laboratory Values (Haematology, Clinical Chemistry, Coagulation and Urinalysis) | Clinically significant change in urinalysis | 0 subjects |
| PICOPREP Tailored Dosing Schedule | Clinically Significant Changes in Laboratory Values (Haematology, Clinical Chemistry, Coagulation and Urinalysis) | Clinically significant change in coagulation | 0 subjects |
| PICOPREP Tailored Dosing Schedule | Clinically Significant Changes in Laboratory Values (Haematology, Clinical Chemistry, Coagulation and Urinalysis) | Clinically significant change in haematology | 0 subjects |
| PICOPREP Tailored Dosing Schedule | Clinically Significant Changes in Laboratory Values (Haematology, Clinical Chemistry, Coagulation and Urinalysis) | Clinically significant change in clinical chem | 0 subjects |
Secondary
Clinically Significant Changes in Vital Signs (Pulse and Blood Pressure)
Mean change from baseline to the end-of-trial was observed for pulse and blood pressure (systolic and diastolic).
Time frame: From baseline (screening) up to day 10 after colonoscopy (inclusive of assessment at each visit)
Population: The Safety analysis set consisted of all treated subjects and was analyzed according to the actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PICOPREP Day-before Dosing Schedule | Clinically Significant Changes in Vital Signs (Pulse and Blood Pressure) | Clinically significant change in pulse | 0 subjects |
| PICOPREP Day-before Dosing Schedule | Clinically Significant Changes in Vital Signs (Pulse and Blood Pressure) | Clinically significant change in blood pressure | 0 subjects |
| PICOPREP Tailored Dosing Schedule | Clinically Significant Changes in Vital Signs (Pulse and Blood Pressure) | Clinically significant change in pulse | 0 subjects |
| PICOPREP Tailored Dosing Schedule | Clinically Significant Changes in Vital Signs (Pulse and Blood Pressure) | Clinically significant change in blood pressure | 0 subjects |
Secondary
Frequency and Intensity of Adverse Events
Time frame: From baseline (screening) up to day 10 after colonoscopy
Population: The Safety analysis set consisted of all treated subjects and was analyzed according to the actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PICOPREP Day-before Dosing Schedule | Frequency and Intensity of Adverse Events | Frequency of all adverse events | 4 subjects |
| PICOPREP Day-before Dosing Schedule | Frequency and Intensity of Adverse Events | Frequency of mild adverse events | 4 subjects |
| PICOPREP Day-before Dosing Schedule | Frequency and Intensity of Adverse Events | Frequency of moderate adverse events | 0 subjects |
| PICOPREP Day-before Dosing Schedule | Frequency and Intensity of Adverse Events | Frequency of severe adverse events | 0 subjects |
| PICOPREP Tailored Dosing Schedule | Frequency and Intensity of Adverse Events | Frequency of severe adverse events | 1 subjects |
| PICOPREP Tailored Dosing Schedule | Frequency and Intensity of Adverse Events | Frequency of all adverse events | 15 subjects |
| PICOPREP Tailored Dosing Schedule | Frequency and Intensity of Adverse Events | Frequency of moderate adverse events | 2 subjects |
| PICOPREP Tailored Dosing Schedule | Frequency and Intensity of Adverse Events | Frequency of mild adverse events | 12 subjects |