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Trial record 46 of 10796 for:    Placebo AND once

Phase 2a Study to Evaluate the Safety/Tolerability and Efficacy of TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks in Ulcerative Colitis (TOP2)

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ClinicalTrials.gov Identifier: NCT02888379
Recruitment Status : Completed
First Posted : September 5, 2016
Last Update Posted : July 7, 2017
Sponsor:
Information provided by (Responsible Party):
Topivert Pharma Ltd

Brief Summary:
A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Safety/Tolerability and Efficacy of TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks in Symptomatic Ulcerative Colitis Patients with Moderate to Severe Disease Activity

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: TOP1288 Drug: Placebo (for TOP1288) Phase 2

Detailed Description:

TOP1288, the first in a new class of agents called narrow spectrum protein kinase inhibitors (NSKIs), is being developed as a novel, non-absorbed treatment for ulcerative colitis (UC). UC is a disease of unknown cause characterised by inflammation of the lining of the large intestine and manifesting with abdominal pain and bloody diarrhoea. TOP1288 given rectally has a local anti-inflammatory action in experimental models of UC.

A Phase I placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study of TOP1288 conducted in 61 healthy volunteers demonstrated that rectal administration of TOP1288 at doses up to 200 mg BID for 4 days was safe and well tolerated, with minimal systemic absorption. TOP1288 200 mg, administered once daily, therefore offers the potential for a safe and effective novel approach to treating patients with this serious condition.

This Phase 2a proof-of-concept study will evaluate the 200 mg daily dose of TOP1288, based on its favourable tolerability in the Phase 1 study. It will be administered as TOP1288 200 mg Rectal Solution compared against Placebo Rectal Solution, which contains all non-active excipients present in the active solution. This is a randomised, double-blind, placebo-controlled multicentre study designed to evaluate the safety/tolerability and efficacy of TOP1288 200 mg Rectal Solution following once-daily bedtime treatment for 4 consecutive weeks. The study will include approximately 40 sites in Europe. Randomization to study treatment will be 2:1, with approximately 40 subjects randomised to TOP1288 and approximately 20 subjects randomised to placebo.

The Screening period will be up to 28 days prior to the first day of dosing with double-blind study treatment (Visit 1). A central reading facility will be used to determine eligibility based upon the Screening flexible sigmoidoscopy.

Visit 2 is scheduled for Day 7 of dosing, and Visit 3 for Day 29 of dosing. There will be a 1-week safety follow-up period after Visit 3. The total duration of study participation for a given subject will be up to ~65 days or 9 weeks


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Safety/Tolerability and Efficacy of TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks in Symptomatic Ulcerative Colitis Patients With Moderate to Severe Disease Activity
Actual Study Start Date : September 2016
Actual Primary Completion Date : June 28, 2017
Actual Study Completion Date : June 28, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TOP1288 200 mg Rectal Solution
TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks
Drug: TOP1288
Placebo Comparator: Placebo Rectal Solution
Placebo (for TOP1288) Rectal Solution Once Daily for 4 Weeks
Drug: Placebo (for TOP1288)



Primary Outcome Measures :
  1. Efficacy as measured by the Mayo Clinic modified endoscopic subscore [ Time Frame: After 4 consecutive weeks of daily bedtime treatment ]

Secondary Outcome Measures :
  1. Safety as measured by adverse events [ Time Frame: To 1 week after the last dose ]
  2. Safety as measured by vital signs [ Time Frame: To 1 week after the last dose ]
  3. Safety as measured by ECGs [ Time Frame: To 1 week after the last dose ]
  4. Safety as measured by clinical laboratory tests [ Time Frame: To 1 week after the last dose ]
  5. Efficacy as measured by Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score [ Time Frame: After 4 consecutive weeks of daily bedtime treatment ]
  6. Efficacy as measured by Partial Mayo Clinic score (i.e., the sum of the endoscopic, rectal bleeding, and stool frequency subscores) [ Time Frame: After 4 consecutive weeks of daily bedtime treatment ]
  7. Efficacy as measured by endoscopic healing (indicated by the Mayo Clinic modified endoscopic subscore) [ Time Frame: After 4 consecutive weeks of daily bedtime treatment ]
  8. Efficacy as measured by rectal bleeding (indicated by the Mayo Clinic rectal bleeding subscore) [ Time Frame: After 4 consecutive weeks of daily bedtime treatment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Diagnosis of UC of at least 3 months duration
  • Active UC with a Partial Mayo Clinic Score of 4 to 8 at randomization

Key Exclusion Criteria:

  • Receiving any rectally administered medication
  • Use of biologic agents within 3 months prior to Screening endoscopy
  • Use of IV corticosteroids within 4 weeks prior to Screening endoscopy
  • Use of oral corticosteroids at a dose >30 mg/day (or budesonide >9 mg/day).
  • Patients who have started receiving immune suppressants within 3 months of the Screening endoscopy should not be included.
  • Known or suspected pancolitis (unless on oral 5-ASA, steroids or permitted immunomodulators)
  • Known or suspected Crohn's disease, indeterminate colitis, microscopic colitis, ischaemic colitis, or radiation-induced colitis, based on medical history, endoscopy, and/or histological findings
  • Extensive (>50%) colonic resection or colectomy, or prior history of toxic megacolon within 3 months of Screening
  • Patient has active serious infection (e.g., sepsis, pneumonia, abscess) or has had a serious infection (resulting in hospitalisation or requiring parenteral antibiotic treatment) within 6 weeks prior to IMP administration
  • Patients testing positive of Clostridium difficile toxin or confirmed with bacterial or parasitical GI infections at Screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02888379


Locations
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Bulgaria
Plovdiv, Bulgaria
Sofia, Bulgaria
Czechia
Brno, Czechia
Litomerice, Czechia
Olomouc, Czechia
Praha, Czechia
Hungary
Budapest, Hungary
Gyongyos, Hungary
Gyor, Hungary
Gyula, Hungary
Szeged, Hungary
Szekesfehervar, Hungary
Vac, Hungary
Latvia
Daugavpils, Latvia
Riga, Latvia
Lithuania
Kaunas, Lithuania
Poland
Bydgoszcz, Poland
Knurow, Poland
Skierniewice, Poland
Sopot, Poland
Warsaw, Poland
Wroclaw, Poland
Ukraine
Kherson, Ukraine
Kyiv, Ukraine
Odessa, Ukraine
Temopil, Ukraine
Zaporizhzhia, Ukraine
United Kingdom
London, United Kingdom
Sponsors and Collaborators
Topivert Pharma Ltd
Investigators
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Principal Investigator: Simon Travis, FRCP Oxford University Hospitals Trust, John Radcliffe Hospital, Oxford, UK,

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Responsible Party: Topivert Pharma Ltd
ClinicalTrials.gov Identifier: NCT02888379     History of Changes
Other Study ID Numbers: TOP1288-TV-02
First Posted: September 5, 2016    Key Record Dates
Last Update Posted: July 7, 2017
Last Verified: July 2017

Additional relevant MeSH terms:
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Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Pharmaceutical Solutions