Trial to Evaluate Efficacy and Safety of Combination of Diacerein and Celecoxib Administered in Patients With Knee OA (DIA IIT_01)

A Prospective, Randomized, Double-blinded, Multi-center, Trial to Evaluate Efficacy and Safety of Combination of Diacerein and Celecoxib Administered Orally in Patients With Knee Osteoarthritis

The purpose of this study is to evaluate the pain relief effect of Co-administration of Diacerein with Celecoxib in patients with knee osteoarthritis compared with single administration of each drug.

Study Overview

• Status: Unknown
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Diacerein; Drug: Celecoxib

Detailed Description

A large epidemiological study in Europe reported that over four-thirds of patients with osteoarthritis received combination therapy with two or more drugs. Approximately 1.5% of patients with osteoarthritis using three or more drugs are using COX-2(Cyclo-oxygenase-2) inhibitors and SYSADOA(Symptomatic slow acting drug), And it has been investigated that much more patients are using the two classes of drugs when the range is extended to other oral NSAIDs other than COX-2 inhibitors. Therefore, considering the characteristics of patients with osteoarthritis, such as basal disease and treatment effects on each type of drug, it is important to find the optimal combination of drugs for each patient characteristics.

There is a previous study using osteoarthritis rat model as a biological basis of diacerein and celecoxib administration. Previous studies have shown that the combined use of Diacerein and Celecoxib improves osteoarthritis.

The purpose of this study is to evaluate the pain relief effect of Co-administration of Diacerein with Celecoxib in patients with knee osteoarthritis compared with single administration of each drug.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yu-na Jo; Phone Number: 82-70-4335-5448; Email: ynjo@symyoo.com
• Study Contact Backup: Name: Sung Woon Yang; Phone Number: 82-31-354-0604; Email: yangsw7@naver.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 08308
    • Recruiting
    • Korea University Guro Hospital
    • Contact: Seon-Mee Kim, MD, PhD; Phone Number: 82-2-2626-3276; Email: ksmpdh@korea.ac.kr
    • Principal Investigator: Seon-Mee Kim, M.D., Ph.D.
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • Seoul st. mary's hospital
    • Contact: Whan-Seok Choi, M.D., Ph.D.; Phone Number: 82-2-2258-6285; Email: fmchs@catholic.ac.kr
    • Principal Investigator: Whan-Seok Choi, M.D., Ph.D
    • Sub-Investigator: Chul-Min Kim, M.D., Ph.D
    • Sub-Investigator: Ji Hyeon Ju, M.D., Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects who voluntarily consented, after listening enough explanation for this study and investigational product.
2. Adult over 50 years of age.
3. At least one of the knee pain VAS score is 40mm or more.

4. Meets the ACR(American College of Rheumatology) criteria for diagnosis. (1) Confirmation of osteophytes on radiographic inspection. (2) One or more of the following three items.

   ① Age> 50 years

   ② Morning stiffness <30 minutes

   ③ Crepitus

5. Patients who require medication for more than 12 weeks due to osteoarthritis symptoms.
6. Those who are able to follow the requirements of this clinical trial, such as being able to trace during the clinical trial period and to read and write the VAS questionnaire.
7. Those who weigh more than 40kg

Exclusion Criteria:

1. Secondary knee osteoarthritis
2. Other inflammatory Knee Osteoarthritis (e.g. gout, rheumatoid arthritis, etc.)
3. Patients presenting with gastroesophageal reflux disease, peptic ulcer.
4. Helicobacter infected patients who have not been treated for eradication (recruitment if negative in re-examination after treatment).
5. Short bowel syndrome that can cause inflammatory bowel disease (ulcerative colitis, Crohn's disease) and drug absorption disorder.
6. Intestinal obstruction syndrome
7. Unexplained abdominal pain
8. ALT(Alanine aminotransferase) level of liver function test exceeded 5 times of reference range
9. Total bilirubin level exceeded 2 mg / dL
10. Serum albumin level less than 2 g / dL
11. Ascites
12. Hepatic encephalopathy
13. Hepatitis B, hepatitis C (excluding healthy carriers) or HIV positive
14. MDRD(Modification of Diet in Renal Disease) Estimated Glomerular filtration rate less than 60 mL / m2
15. Patients with hyperkalemia (over 5.5 meq / L)
16. history of asthma, acute rhinitis, nasal polyps, angioedema, urticaria or allergic reactions to aspirin or other non-steroidal anti-inflammatory drugs(including COX-2 inhibitors).
17. Malignant tumors other than basal cell or squamous cell carcinoma of the skin, CIN(Cervical Intraepitherial Neoplasia) and CIS(Carcinoma in situ) of the cervix, and intraepithelial carcinoma of other areas Within 5 years of consent date.
18. Medical history of hypersensitivity to the components of the investigational products. (The components of test drug 1 and 2, including the Rhein-based drug)
19. Patients with an allergic reaction to sulfonamide.
20. Patients with galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption.
21. Subjects who have not reached the prescribed period after receiving contraindicated medication or treatment before participation in this clinical trial.
22. Patients receiving contraindicated medication.
23. Alcohol and other drug abuse cases based on 6 months before screening.
24. Pregnant women or nursing mothers who are not willing to stop breastfeeding.

25. Female who do not fall into one or more of the following categories(In other words, only the following female can participate:)

    • (1) Menopause (non-therapy-induced amenorrhea of more than 12 months) Female
    • (2) Female infertility due to surgery (no ovaries and / or uterus)
    • (3) If you have sexual intercourse with only one male partner who has been confirmed to have no semen after fertilization.
    • (4) Female subjects who agreed to abstinence during the clinical trial period.
    • If the subject is assured of an abstinence throughout the trial period.(e.g. clergy)
    • However, intermittent abstinence (eg, contraception using ovulation period, symptothermal) or coitus interrupts is not a case of consent for abstinence.
    • (5) For women of childbearing age, the following methods or methods of contraception use the effective method of contraception to be used during the period of this clinical trial:
    • Oral contraceptive
    • The contraceptive patch
    • Intra uterine device (IUD)
    • contraceptive implant
    • contraceptive injection
    • intrauterine hormonal apparatus
    • Tubal ligation and infertility surgery
26. If 30 days have not elapsed after the date of signing of the previous clinical trial or currently participating in other clinical trials.
27. Patients who are scheduled for surgery during the clinical trial period or who have difficulties in completing the protocol during this clinical trial due to other reasons.
28. In addition to the above, other diseases that the investigator judges to be inappropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Co-administration group; Co-administration of Diacerein 50mg, Celecoxib 100mg.	Drug: Diacerein; For 12 weeks, administered twice a day by oral.; Drug: Celecoxib; For 12 weeks, administered twice a day by oral.
Active Comparator: Single administration group 1; Single administration of Diacerein 50mg and placebo.	Drug: Diacerein; For 12 weeks, administered twice a day by oral.
Active Comparator: Single administration group 2; Single administration of Celecoxib 100mg and placebo.	Drug: Celecoxib; For 12 weeks, administered twice a day by oral.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pain VAS score	Changes in pain VAS(Visual analogue scale) score before and after 12 weeks of drugs administration. (No pain score: 0, Worst pain score: 100)	12 weeks after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pain NRS score	Changes in pain NRS(Numeric rating scale) score before and after 12 weeks of drugs administration. (No pain score: 0, Worst pain score: 10)	12 weeks after randomization
WOMAC index score	Changes in WOMAC(Western Ontario and mcmaster Universities Osteoarthritis Index) index score before and after 12 weeks of drugs administration (possible score range, Pain: 0-20, Stiffness: 0-8, Physical function: 0-68; Total Score range: 0-96 ('none' to 'extreme'))	12 weeks after randomization
GSRS index score	Changes in GSRS(Gastrointestinal symptom rating scale) index score before and after 12 weeks of drugs administration. (Score range: 0-45 ('none' to 'extreme'))	12 weeks after randomization

Collaborators and Investigators

• Sponsor: Whan-Seok Choi
• Collaborators: Korea University Guro Hospital
• Investigators: Principal Investigator: Whan-Seok Choi, MD, PhD, Seoul st. mary's hospital; Principal Investigator: Seon-Mee Kim, MD, PhD, Korea University Guro Hospital

Publications and helpful links

General Publications

• Li Z, Meng D, Li G, Xu J, Tian K, Li Y. Celecoxib Combined with Diacerein Effectively Alleviates Osteoarthritis in Rats via Regulating JNK and p38MAPK Signaling Pathways. Inflammation. 2015 Aug;38(4):1563-72. doi: 10.1007/s10753-015-0131-3.
• Martel-Pelletier J, Pelletier JP. Effects of diacerein at the molecular level in the osteoarthritis disease process. Ther Adv Musculoskelet Dis. 2010 Apr;2(2):95-104. doi: 10.1177/1759720X09359104.
• Panova E, Jones G. Benefit-risk assessment of diacerein in the treatment of osteoarthritis. Drug Saf. 2015 Mar;38(3):245-52. doi: 10.1007/s40264-015-0266-z.
• Nicolas P, Tod M, Padoin C, Petitjean O. Clinical pharmacokinetics of diacerein. Clin Pharmacokinet. 1998 Nov;35(5):347-59. doi: 10.2165/00003088-199835050-00002.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2018
• Primary Completion (Anticipated): January 2, 2019
• Study Completion (Anticipated): January 2, 2019

Study Registration Dates

• First Submitted: January 12, 2018
• First Submitted That Met QC Criteria: January 12, 2018
• First Posted (Actual): January 19, 2018

Study Record Updates

• Last Update Posted (Actual): February 26, 2018
• Last Update Submitted That Met QC Criteria: February 22, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Knee Osteoarthritis; Diacerein
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib; Diacetylrhein
• Other Study ID Numbers: DIA IIT_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No