Localized Primary Osteoarthritis of Hip, Localized Primary Osteoarthritis of Knee
Conditions
Keywords
COX-1, COX-2, carbonic anhydrase, anti-inflammatory, Cyclooxygenase Inhibitors, Polmacoxib
Brief summary
* 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.
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)
Interventions
DRUGCG100649
2 mg capsule
DRUGCelecoxib
200 mg capsule
DRUGPlacebo
Mimic for CG100649 2 mg capsule and for celecoxib 200 mg capsule
Sponsors
CrystalGenomics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in WOMAC-Pain Subscale | Baseline, Week 6 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of the WOMAC-physical Function Subscale at Week 3 and 6 From Pre-dose Baseline | Baseline, Week 3 and Week 6 | 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. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo capsule by mouth, once a day for 6 weeks (Treatment Phase), followed by CG100649 2 mg, oral, for 18 weeks (Safety Phase) | 71 |
| 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) | 146 |
| 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) | 145 |
| Total | 362 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 13 | 5 |
| Overall Study | Lack of Efficacy | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 5 | 4 |
| Overall Study | Withdrawal by Subject | 4 | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo | CG100649 | Celecoxib | Total |
|---|---|---|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 8.97 | 62.5 years STANDARD_DEVIATION 7.52 | 62.1 years STANDARD_DEVIATION 7.59 | 62.4 years STANDARD_DEVIATION 7.83 |
| Sex: Female, Male Female | 61 Participants | 125 Participants | 123 Participants | 309 Participants |
| Sex: Female, Male Male | 10 Participants | 21 Participants | 22 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 71 | 20 / 146 | 15 / 145 |
| serious Total, serious adverse events | 1 / 71 | 2 / 146 | 1 / 145 |
Outcome results
Primary
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.
Time frame: Baseline, Week 6
Population: Intent-to-Treat (ITT) population (Baseline Observation Carried Forward (BOCF))
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in WOMAC-Pain Subscale | Week 6 | 24.2 units on a scale | Standard Deviation 7.41 |
| Placebo | Change in WOMAC-Pain Subscale | Baseline | 26.8 units on a scale | Standard Deviation 4.58 |
| Placebo | Change in WOMAC-Pain Subscale | Change From Baseline | -2.5 units on a scale | Standard Deviation 6.73 |
| CG100649 2 mg | Change in WOMAC-Pain Subscale | Week 6 | 22.7 units on a scale | Standard Deviation 8.71 |
| CG100649 2 mg | Change in WOMAC-Pain Subscale | Baseline | 27.9 units on a scale | Standard Deviation 5.01 |
| CG100649 2 mg | Change in WOMAC-Pain Subscale | Change From Baseline | -5.3 units on a scale | Standard Deviation 7.11 |
| Celecoxib 200 mg | Change in WOMAC-Pain Subscale | Baseline | 27.7 units on a scale | Standard Deviation 5.08 |
| Celecoxib 200 mg | Change in WOMAC-Pain Subscale | Change From Baseline | -5.8 units on a scale | Standard Deviation 6.67 |
| Celecoxib 200 mg | Change in WOMAC-Pain Subscale | Week 6 | 21.9 units on a scale | Standard Deviation 7.65 |
Comparison: The primary efficacy outcome measure is the change in the WOMAC-Pain Subscale in the index joint at Week 6 vs. pre-dose Baseline and was analyzed using a mixed effect ANCOVA. Statistical tests to determine superiority between two treatment arms, CG100649 2 mg and placebo, are two-sided, and Non-inferiority between two treatment arms, CG100649 2 mg and celecoxib 200 mg is based on a one-sided 97.5% confidence interval of the difference.p-value: 0.011ANCOVA
p-value: 0.425ANCOVA
Secondary
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.
Time frame: Baseline, Week 3 and Week 6
Population: Intent-to-Treat (ITT) (BOCF)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change of the WOMAC-physical Function Subscale at Week 3 and 6 From Pre-dose Baseline | Week 3 | -5.7 units on a scale |
| Placebo | Change of the WOMAC-physical Function Subscale at Week 3 and 6 From Pre-dose Baseline | Week 6 | -7.9 units on a scale |
| CG100649 2 mg | Change of the WOMAC-physical Function Subscale at Week 3 and 6 From Pre-dose Baseline | Week 3 | -13.7 units on a scale |
| CG100649 2 mg | Change of the WOMAC-physical Function Subscale at Week 3 and 6 From Pre-dose Baseline | Week 6 | -14.3 units on a scale |
| Celecoxib 200 mg | Change of the WOMAC-physical Function Subscale at Week 3 and 6 From Pre-dose Baseline | Week 3 | -10.7 units on a scale |
| Celecoxib 200 mg | Change of the WOMAC-physical Function Subscale at Week 3 and 6 From Pre-dose Baseline | Week 6 | -14.9 units on a scale |