A safety and efficacy study of a novel formulation of prednisolone metasulfobenzoate (predocol) in the induction of remission and maintenance in patients with ulcerative colitis

ISRCTN ISRCTN14133410
DOI https://doi.org/10.1186/ISRCTN14133410
Protocol serial number Predocol 9804
Sponsor Flexpharm Ltd. (UK)
Funder Enterotech Ltd (Jersey)
Submission date
01/03/2006
Registration date
28/04/2006
Last edited
06/08/2008
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Jonathan M. Rhodes
Scientific

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

Study information

Primary study designInterventional
Study designMulticentre, randomised, double-blind study
Secondary study designRandomised controlled trial
Scientific title
Study acronymTOPPIC
Study objectivesThe 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(s)Approved by the Central Ethics Committees of Southeast Multicentre Research Ethics Committee (MREC) and Kent and Medway Strategic Health Authority, Preston Hall, 1999
Health condition(s) or problem(s) studiedAcute exacerbations of ulcerative colitis
InterventionActive 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 typeDrug
PhaseNot Specified
Drug / device / biological / vaccine name(s)Prednisolone metasulfobenzoate (predocol), oral prednisolone
Primary outcome measure(s)

Efficacy:
The primary criterion for efficacy was the patient’s 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.

Key secondary outcome measure(s)

Efficacy:
1. Secondary criteria were the physician’s global VAS assessment of patient’s progress
2. Physician’s 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.

Completion date01/02/2005

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexAll
Target sample size at registration180
Key inclusion criteriaTo 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
Key exclusion criteriaPatients 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
Date of first enrolment01/11/2000
Date of final enrolment01/02/2005

Locations

Countries of recruitment

  • United Kingdom
  • England
  • Ireland

Study participating centre

Henry Wellcome Laboratory of Molecular & Cellular Gastroenterology
Liverpool
L69 3BX
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article Results 01/02/2008 Yes No
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