Study of SI000413 in Knee Osteoarthritis Patients

Eight-week, Multi-centre, Dose-response, Double Blind, Placebo-controlled, Randomized, Parallel-group, PhaseⅡ Trial to Evaluate Efficacy and Safety of SI000413 in Patients With Knee Osteoarthritis

The purpose of this study is to evaluate efficacy and safety of SI000413 in patients with knee osteoarthritis by orally administration and to determine optimal dose.

Study Overview

• Status: Unknown
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: SI000413; Drug: microcrystalline cellulose

Detailed Description

This is a dose-response, double blind , placebo-controlled study. All patients are required to have 2 weeks washout period from prior medication. Subjects will discontinue current medications 2 weeks prior to randomization. Among those who meet the inclusion criteria, only subjects recording visual analogue scale(VAS) of higher than 40mm(VAS range from 0mm(no pain) to 100mm(unbearable pain)) are enrolled in this study.

Subjects meeting screening criteria will be randomized to receive 8 weeks dosing of an active dose of SI000413 or placebo.

• Study Type: Interventional
• Enrollment (Anticipated): 152
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Hoegi-dong, Dongdaemun-gu
    • Seoul, Hoegi-dong, Dongdaemun-gu, Korea, Republic of, 130-872
      • Recruiting
      • KyungHee University Medical Center
  • Woncheon-dong Yeongtong-gu, Suwon
    • Gyeonggi-do, Woncheon-dong Yeongtong-gu, Suwon, Korea, Republic of, 443-721
      • Recruiting
      • Ajou University Medical Center
      • Principal Investigator: We-Yeon Won, MD
  • Yongon-dong, Chongno-gu
    • Seoul, Yongon-dong, Chongno-gu, Korea, Republic of, 110-744
      • Recruiting
      • Seoul National University Hospital
      • Principal Investigator: Myung-Chul Lee, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females, 35-75 years old

2. Subjects must have a clinical or radiographic diagnosis of primary OA of the knee (diagnosed according to the ACR)

   • The presence of knee pain

   • At least one of the following

     • age older than 50 years
     • morning stiffness lasting less than 30 minutes
     • crepitus with motion
3. Subjects must have been symptomatic for at least 3 months prior to enrollment.
4. Subjects must be required to have experienced a pain intensity of at least 40mm on a 100-mm visual analogue scale in the most severely affected joint during the 24 hours prior to randomization.

5. Adequate liver and kidney function

   • Adequate liver function : SGOT, SGPT must be within 1.5 x normal limit
   • Adequate kidney function : Serum creatinine must be within 1.5 x normal limit
6. Subjects must be able to read, understand and follow the study instructions
7. Subjects must agree to informed consent spontaneously.

Exclusion Criteria:

1. Subjects who are not using adequate birth control.
2. Pregnant or breast-feeding.
3. Subjects requiring Knee surgery within 1 year of screening anticipating any need for a surgical procedure during the study.
4. Secondary OA patients
5. Similar OA patients(ex. rheumatic arthritis, bursitis etc)
6. Treatment with intra-articular injections of systemic corticosteroids or hyaluronic acid in the prior 3 months.
7. Use of drugs or psychotropic medicine(methadone maintenance program, codeine, tramadol hydrochloride)
8. Anemia or coagulant disorder
9. Use of anticoagulants or lithium
10. Use of misoprostol or H2-blocker(including anti ulcer medicine)
11. Presence or history of gastrointestinal bleeding within the past 1 year.
12. Subjects who have serious problem with cardiovascular, respiratory, endocrine, central nervous or History of neurotic mental.
13. Active malignancy of any type(ex. lymphoma, multiple myeloma etc)
14. Use of any medication that will affect pain perception during the study period; physical therapy, corticosteroids, NSAIDs, asprin, topical analgesics.
15. Use of glucosamine, chondroitin during the study period.
16. Change of concomitant dose/use within 4 weeks.
17. Known allergy or hypersensitivity to medicine.
18. Subjects received hormone replacement therapy.
19. Use of any other investigational drug within 1 month prior to screening.
20. Investigators determines that it is not appropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SI000413 400mg; tablet, SI000413 200mg bid	Drug: SI000413; 1 Tablet = 200mg, (400mg, 600mg or 800mg vs. placebo) for 8weeks
EXPERIMENTAL: SI000413 600mg; tablet, SI000413 200mg tid	Drug: SI000413; 1 Tablet = 200mg, (400mg, 600mg or 800mg vs. placebo) for 8weeks
EXPERIMENTAL: SI000413 800mg; SI000413 200mg, 2T bid	Drug: SI000413; 1 Tablet = 200mg, (400mg, 600mg or 800mg vs. placebo) for 8weeks
PLACEBO_COMPARATOR: placebo; placebo 2T tid for 8 weeks	Drug: microcrystalline cellulose; identical number of tablets to active drug groups; Other Names: SI000413 placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
K-WOMAC	The primary endpoint will be the change in the sum of the K-WOMAC OA index at Visit 6(8 weeks) vs. baseline(Visit 2, 0 week).	Visit 6(8 week), baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
knee pain intensity assessment	The change from baseline to each day(4 week and 8 week). Subjects assess knee pain intensity by using 100mm VAS at each time.	baseline, Visit 4(4 week), Visit 6(8 week)
Global assessment(regarding to disease activity)	The change from Visit 4 to Visit 6 using 100mm VAS. Each patient and investigator assess by using 100mm VAS.	Visit 4(4 week), Visit 6(8 week)
K-WOMAC each domain assessment	The change from Visit 6(8 weeks) vs. baseline(Visit 2, 0 week) in the K-WOMAC each domain score. * K-WOMAC 3 domains: pain domain, stiffness domain, physical function domain	baseline, Visit 6(8 week)
ESR & hs-CRP	The change from baseline to each day(Visit 4, Visit 6) using laboratory test.	baseline, Visit 4(4 week), Visit 6(8 week)

Collaborators and Investigators

• Sponsor: Dong-A Pharmaceutical Co., Ltd.
• Investigators: Study Chair: Yoon-Jae Cho, MD, KyungHee University Medical Center; Principal Investigator: Myung-Chul Lee, MD, Seoul National University Hospital; Principal Investigator: We-Yeon Won, MD, Ajou University Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (ANTICIPATED): December 1, 2013
• Study Completion (ANTICIPATED): December 1, 2013

Study Registration Dates

• First Submitted: January 31, 2012
• First Submitted That Met QC Criteria: February 2, 2012
• First Posted (ESTIMATE): February 3, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): August 13, 2013
• Last Update Submitted That Met QC Criteria: August 12, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: SI000413_OA_Ⅱ