Therapeutic Study of ONO-4819CD for Ulcerative Colitis

Ulcerative Colitis Clinical Trial

Official title:

A Randomized, Placebo-Controlled Trial of ONO-4819CD for Treatment of Mild to Moderate Ulcerative Colitis.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00296556
• Other study ID #: TRC05PG-II-1
• Status: Terminated
• Phase: Phase 2
• First received: February 24, 2006
• Last updated: April 27, 2009
• Start date: February 2006
• Est. completion date: March 2008

Study information

• Verified date: April 2009
• Source: Kyoto University, Graduate School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate whether ONO-4819CD is safe and effective in the treatment of mild to moderate ulcerative colitis.

Description:

Ulcerative colitis is a relapsing disease of unknown cause characterized by bloody diarrhea. Therapy usually involves 5-aminosalicylates, corticosteroids and immunosuppressants. However, steroid resistance and dependency can become problematic. Immunosuppressive drugs, such as azathioprine, are beneficial but may have serious side effects. Therefore, new therapeutic approach is needed.

Prostaglandin E2 is one of the prostanoids, which is involved with innate immunity. PGE2 induces oral tolerance to specific antigen in the small intestine and downregulates the production and release of proinflammatory cytokines by macrophages and neutrophils. Accordingly, PGE2 is considered to be the mediator of mucosal protection.

Recently, it was elucidated that disruption of EP4 gene, which is one of PGE receptors, caused severe colitis in mice. Moreover, EP4-selective agonist (AE1-734) was also revealed to ameliorate severe dextran sodium sulfate-induced colitis in mice. We therefore examined the effects of 2 weeks intravenous EP4-selective agonist therapy for patients with mild to moderate ulcerative colitis.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: March 2008
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

1. Clinical diagnosis of ulcerative colitis

2. Mild to moderate ulcerative colitis refractory to 5-aminosalicylates therapy.

3. 20 years and above

4. Must obtain written informed consent

Exclusion Criteria:

1. Corticosteroids therapy within two weeks before enrollment

2. Immunosuppressive therapy within three months before enrollment

3. Leukocytapheresis therapy within one month before enrollment

4. Blood transfusion within two weeks before enrollment

5. Impaired renal function

6. Impaired hepatic function

7. Uncontrolled hypertension/hypotension

8. Uncontrolled arrhythmia

9. Impaired cardiac function

10. Cancer

11. Uncontrolled diabetes

12. Interstitial pneumonia

13. Glaucoma

14. History of colon resection

15. Infectious diseases needing medical treatments

16. Drug allergy

17. Pregnancy

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Rivenprost (drug)

Locations

Country	Name	City	State
Japan	Kyoto University, Graduate School of Medicine	Kyoto

Sponsors (2)

Lead Sponsor	Collaborator
Kyoto University, Graduate School of Medicine	National Institute of Biomedical Innovation

Country where clinical trial is conducted

Japan, 

References & Publications (2)

Kabashima K, Saji T, Murata T, Nagamachi M, Matsuoka T, Segi E, Tsuboi K, Sugimoto Y, Kobayashi T, Miyachi Y, Ichikawa A, Narumiya S. The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut. J Clin Invest. 2002 Apr;109(7):883-93. — View Citation

Morimoto K, Sugimoto Y, Katsuyama M, Oida H, Tsuboi K, Kishi K, Kinoshita Y, Negishi M, Chiba T, Narumiya S, Ichikawa A. Cellular localization of mRNAs for prostaglandin E receptor subtypes in mouse gastrointestinal tract. Am J Physiol. 1997 Mar;272(3 Pt 1):G681-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Remission evaluated by DAI scores at 14 and 28 days
Secondary	Improvement by DAI scores; Change in DAI scores; CAI scores at 3, 7, 14 and 28 days; Colonoscopic and histopathological scores at 14 and 28 days; Clinical severity and symptom scores at 7, 14 and 28 days; Cytokines at 7, 14 and 28 days; Adverse effects.