Phase III Study of CG100649 in Osteoarthritis Patients

A Double-blind, Randomized, Multicenter, Active- and Placebo-Controlled Phase III Study to Evaluate the Efficacy and Safety of CG100649 in Osteoarthritis Patients

• 6-week Efficacy Study The objective of this study is to prove the safety and non-inferiority of analgesic efficacy of CG100649 2 mg vs. celecoxib 200 mg, and analgesic superiority of CG100649 2 mg vs. placebo, when administered once a day in patients with osteoarthritis of the hip or knee over the 6 week Treatment period. The primary efficacy parameter is the difference from Baseline to Week 6 in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC)-Pain subscale.
• Extended Safety Study The objective of the Extended Safety Study is to collect a total of 24 weeks of safety data for CG100649 including the initial 6 weeks of safety data, and an additional 18 weeks of safety data for those subjects who agree on the consent form to continue into the Extended Safety Study. Subjects will be administered CG100649 2 mg only during 18 weeks of Extended Safety Study.

Study Overview

• Status: Completed
• Conditions: Localized Primary Osteoarthritis of Hip; Localized Primary Osteoarthritis of Knee
• Intervention / Treatment: Drug: Celecoxib; Drug: Placebo; Drug: CG100649

Detailed Description

1. Number of Subjects: 350 (2:2:1 ratio of experimental vs. active comparator vs. placebo comparator)
2. Adverse Events will be coded to preferred term and body system using the Medical Dictionary for Regulatory Activities (MedDRA)

• Study Type: Interventional
• Enrollment (Actual): 362
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of
    • Kyungpook National University Hospital
  • Daejeon, Korea, Republic of, 301-721
    • Chungnam National University Hospital
  • Goyang-si, Korea, Republic of, 410-719
    • NHIC Ilsan Hospital
  • Incheon, Korea, Republic of
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 135-720
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of, 137-701
    • Seoul St. Mary'S Hospital
  • Seoul, Korea, Republic of
    • Inje University Seoul Paik Hospital
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 156-707
    • Boramae Medical Center
  • Seoul, Korea, Republic of, 133-792
    • Hanyang University Hospital
  • Seoul, Korea, Republic of, 158-710
    • Ewha Womans University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria (abbreviated)

1. Males or females, age 20 years or above, able and willing to provide written informed consent
2. Knee or Hip OA diagnosed according to American College of Rheumatology guidelines
3. Chronic pain for ≥3 months from OA
4. BP [systolic 90-140 mmHg, diastolic 50-90 mmHg] and pulse rate [resting 40-100 bpm].
5. WOMAC-Pain score in the index joint must be between 4-8 on a 0-10 numerical rating scale
6. Blood chemistry must be within 2x normal range
7. Urinalysis must be within normal limits; minor deviations are acceptable
8. Subjects and their sexual partners must agree to use double barrier contraception during the study period and for 3 months afterward, or be at least one year post- menopause, or provide proof of surgical sterility
9. For prior non-steroidal inflammatory drug (NSAID) users only, the subject has a history of positive therapeutic benefit
10. Subject is willing to limit alcohol intake to 2 or less drinks per day during study and the follow-up period
11. Subjects must be able to read, understand and follow study related documents.

Exclusion Criteria (abbreviated)

1. Use of any analgesics except the study medication or acetaminophen at any time
2. Use of any medications for ongoing chronic symptoms, or psychiatric disorders that could significantly diminish the cognitive ability or cause behavioral changes that would prevent the subject from complying with study procedures.
3. Subject is legally incompetent, or has active psychosis, or significant emotional problems which are sufficient to interfere with the conduct of the study
4. Use of anticoagulants (aspirin, warfarin, heparin, etc.) within 2 weeks of V1
5. Previous history of hypersensitivity or allergy to NSAIDs, COX-2 inhibitors, carbonic anhydrase inhibitors, sulfa drugs, aspirin, or acetaminophen/paracetamol
6. Subjects requiring knee or hip arthroplasty within 2 months of screening or anticipating any need for a surgical procedure on the index joint during the study
7. Diagnosed or treated for active GI ulcer, GI bleeding, ulcerative colitis, or severe renal, hepatic, or coagulant disorder within 6 months prior to randomization
8. History of nasal polyps, bronchospasm, urticaria, or anaphylactic shock
9. Subjects who have had surgery on the affected joint within 6 months prior to the study and subjects with a prosthesis at the index joint
10. Pregnant or breast-feeding, or expecting to conceive within the projected duration of the study
11. Subjects who are currently participating or have participated in other clinical studies within 4 weeks of screening or in any other clinical trial evaluating NSAIDs or COX-2 inhibitors within 6 months of screening
12. Subjects who have received even one dose of rofecoxib or etoricoxib at any time in their life
13. History of congestive heart failure with a status of New York Heart Association II-IV, ischemic heart disease, uncontrolled hypertension, peripheral arterial disease, cerebrovascular disease or subjects who have one of these diseases
14. Current user of recreational or illicit drugs or has had a recent history (1 year) of drug or alcohol abuse or dependence
15. History of neoplastic disease or chemotherapy within 5 years of V1, with the exception of non-metastatic skin cancer that has been completely cured
16. Subjects with gout, pseudogout, inflammatory arthritis, Paget's disease of bone, chronic pain syndrome, fibromyalgia, or another major joint disease
17. Subjects using i.v, i.m., or oral corticosteroids, i.a. steroids or hyaluronic acid injections within 1 month of V1
18. Subjects receiving a Chinese traditional arthritis treatment within 1 week of V1
19. Subjects who are not suitable to participate in the study by the investigator's clinical decision

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Celecoxib; Celecoxib 200 mg by mouth, once a day for 6 weeks (Treatment Phase), followed by CG100649 2 mg, oral, for 18 weeks (Safety Phase)	Drug: Celecoxib; 200 mg capsule; Other Names: Celebrex
Placebo Comparator: Placebo; Placebo capsule by mouth, once a day for 6 weeks (Treatment Phase), followed by CG100649 2 mg, oral, for 18 weeks (Safety Phase)	Drug: Placebo; Mimic for CG100649 2 mg capsule and for celecoxib 200 mg capsule
Experimental: CG100649; CG100649 2 mg capsule by mouth, once a day for 6 weeks (Treatment Phase); CG100649 2 mg capsule by mouth, once a day for 18 weeks (Safety Phase)	Drug: CG100649; 2 mg capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in WOMAC-Pain Subscale	Western Ontario and McMaster Universities (WOMAC) OA index. Version 3.1 of the WOMAC knee and hip osteoarthritis index translated in Korean language will be used for each site enrolled in the trial. The numerical rating scale version of the WOMAC-Pain subscale was used, i.e., with the subject assessing each question by a 11-point (0-10) numerical rating scale, and the total pain score being represented by the sum of the 5 component item scores. A higher WOMAC score represented worse symptom severity, with 50 being the worst possible total score.	Baseline, Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of the WOMAC-physical Function Subscale at Week 3 and 6 From Pre-dose Baseline	Western Ontario and McMaster Universities (WOMAC) OA index. Version 3.1 of the WOMAC knee and hip osteoarthritis index translated in Korean language will be used for each site enrolled in the trial. The 24 questions, which measure with 0-10 point numerical rating scale (NRS) with a maximum of 240 points to evaluate "Pain (5 questions)," "Stiffness (2 questions)," and "Physical Function (17 questions)" in WOMAC 3.1. Total scores for WOMAC-physical function is from 0 to 170 points. A higher WOMAC score represented worse symptom severity.	Baseline, Week 3 and Week 6

Collaborators and Investigators

• Sponsor: CrystalGenomics, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: January 8, 2013
• First Submitted That Met QC Criteria: January 9, 2013
• First Posted (Estimate): January 10, 2013

Study Record Updates

• Last Update Posted (Actual): February 15, 2023
• Last Update Submitted That Met QC Criteria: February 13, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: anti-inflammatory; COX-2; carbonic anhydrase; Cyclooxygenase Inhibitors; COX-1; Polmacoxib
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Osteoarthritis, Hip; 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
• Other Study ID Numbers: CG100649-3-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This medication already got NDA approval in Korea