Contact information
Type
Scientific
Primary contact
Prof Jonathan M. Rhodes
ORCID ID
Contact details
Henry Wellcome Laboratory of Molecular & Cellular Gastroenterology
Department of Medicine
University of Liverpool
Crown Street
Liverpool
L69 3BX
United Kingdom
j.m.rhodes@liverpool.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Predocol 9804
Study information
Scientific title
Acronym
TOPPIC
Study hypothesis
The primary objective of the study was to assess the safety of predocol, a controlled delivery formulation of orally administered prednisolone metasulfobenzoate, administered at two dose levels compared with oral prednisolone and with each other, in patients with ulcerative colitis.
Ethics approval
Approved by the Central Ethics Committees of Southeast Multicentre Research Ethics Committee (MREC) and Kent and Medway Strategic Health Authority, Preston Hall, 1999
Study design
Multicentre, randomised, double-blind study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Acute exacerbations of ulcerative colitis
Intervention
Active drug:
Predocol (prednisolone metasulphobenzoate) 40 mg or 60 mg were provided as four (+2 placebo) or six capsules oral daily with appropriate overcoating to retain blinding. Dosing was for six months.
Active comparator:
EC prednisolone in a reducing dosage regimen, six capsules were provided to retain blinding (starting dose of 40 mg reducing to 5 mg over the two-month treatment period according to a fixed protocol). Dosing with the EC prednisolone was for two months of the overall six months of the study with placebo being provided for the remaining four months.
Intervention type
Drug
Phase
Not Specified
Drug names
Prednisolone metasulfobenzoate (predocol), oral prednisolone
Primary outcome measure
Efficacy:
The primary criterion for efficacy was the patients global visual analogue scale (VAS) assessment of symptoms.
Safety:
The primary safety criterion was the patient's overall assessment of the severity of steroid-related side-effects during the acute phase of the study.
Secondary outcome measures
Efficacy:
1. Secondary criteria were the physicians global VAS assessment of patients progress
2. Physicians clinical assessment of ulcerative colitis symptoms (Powell-Tuck)
3. Sigmoidoscopy grading
4. Number of patients requiring escape therapy
5. Time to stopping medication due to disease exacerbation
6. Health status and healthcare usage
Safety:
Secondary criteria were the severity of listed side-effects and the incidence of adverse experiences, HbA1c, C-reactive protein (CRP), testosterone or oestrogen, abnormal laboratory data and findings of clinical concern. Patients at selected centres were also assessed for bone mineral density and osteocalcin levels.
Overall trial start date
01/11/2000
Overall trial end date
01/02/2005
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
To be enrolled in the study patients were required to meet the following inclusion criteria:
1. Have histologically confirmed ulcerative colitis considered suitable for therapeutic treatment with predocol or prednisolone
2. Have active rectal inflammation extending at least to the proximal descending sigmoid junction, which was categorised as mild, moderate or severe, using the Baron Grade for mucosal appearance at sigmoidoscopy as follows: 0: normal; 1: erythema or granularity only. No contact bleeding; 2: friable but no spontaneous bleeding; 3: spontaneous bleeding
3. Be aged 18 to 85 years
4. Give written informed consent to participate
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
180
Participant exclusion criteria
Patients were excluded from the study if any of the following applied:
1. Severe fulminating ulcerative colitis
2. Having taken more than three daily doses of oral steroid therapy or any steroid enemas in the month before study entry
3. Immunosuppressive therapy other than maintenance therapy with azathioprine
4. Pregnant and nursing mothers
5. Significant renal, hepatic, cardiovascular or neuropsychiatric impairment, diabetes or alcohol abuse
6. The concomitant use of drugs likely to suppress daytime gastric acidity (proton pump inhibitors or large doses of H2 antagonists)
7. Crohn's disease
8. Unlikely to be able to comply with the protocol
9. Female patients of child-bearing potential unless using a reliable form of contraception throughout the period of the study
10. Participation in an experimental drug study in the preceding three months
11. Previous resistance to conventional daily 40 mg prednisolone over a period of two weeks
Recruitment start date
01/11/2000
Recruitment end date
01/02/2005
Locations
Countries of recruitment
Ireland, United Kingdom
Trial participating centre
Henry Wellcome Laboratory of Molecular & Cellular Gastroenterology
Liverpool
L69 3BX
United Kingdom
Funders
Funder type
Industry
Funder name
Enterotech Ltd (Jersey)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
Results in http://www.ncbi.nlm.nih.gov/pubmed/17988236
Publication citations
-
Results
Rhodes JM, Robinson R, Beales I, Pugh S, Dickinson R, Dronfield M, Speirs CJ, Wilkinson P, Wilkinson SP, Clinical trial: oral prednisolone metasulfobenzoate (Predocol) vs. oral prednisolone for active ulcerative colitis., Aliment. Pharmacol. Ther., 2008, 27, 3, 228-240, doi: 10.1111/j.1365-2036.2007.03569.x.