E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary osteoarthritis (OA) of the knee or hip |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020108 |
E.1.2 | Term | Hips osteoarthritis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023476 |
E.1.2 | Term | Knee osteoarthritis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this trial is to evaluate the safety and efficacy of 3 loading and maintenance dose levels of CG100649 administered for 21 days in the treatment of osteoarthritis pain. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males, age 18-75 years old, able and willing to provide written informed consent to participate in the study;
2. Body mass index (BMI) 19-35 kg/m2;
3. Good health as determined by medical history, physical examination, 12-lead electrocardiogram (ECG), and clinical laboratory evaluations with the exception of osteoarthritic disease;
4. Normal blood pressure (BP) [systolic BP 90-140 mmHg, diastolic BP 50-90 mmHg] and heart rate (HR) [resting HR 45-90 beats per minute (bpm)] without medication;
5. Clinical chemistry profile including electrolytes, alkaline phosphatase (ALK), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), creatinine, and urea must be within 2x normal range without medication;
6. Urinalysis including urinary creatinine must be within 2x normal limits (minor deviations are acceptable per the clinical decision of the Principal Investigator at each site);
7. OA must be confirmed by radiographs obtained within the past 20 years and diagnosed according to American College of Rheumatology (ACR) guidelines; subjects must qualify as ACR global functional status I, II, or III (excluding IV) and Kellgren-Lawrence grade 1, 2 or 3 (excluding grades 0 and 4);
8. Subjects must have had chronic pain for ≥3 months from OA;
9. Subjects must have been receiving stable oral doses of NSAIDs or COX-2 inhibitors at least 3 days per week for one month or longer;
10. Subjects may take paracetamol (acetaminophen; ≤2g/day) for breakthrough pain;
11. During the washout period, the average daily pain intensity (DPI) score must be between 4 and 8 on a 0-10 numerical rating scale for at least 3 days, and no greater than 9 for more than 1 day, in the last 5 days prior to randomization per Baseline pain diary;
12. Subjects must be able to read, understand and follow the study instructions, including completion of pain intensity rating scales and the ability to maintain a pain and symptom diary on a daily basis;
13. Subjects and their sexual partners must agree to use double barrier contraception during the study period and for 2 months afterward or provide proof of surgical sterility. Double barrier contraception may include, but is not limited to, using a male condom with spermicide; having a female sexual partner who agrees to use an IUD with spermicide, a female condom with spermicide, a diaphragm with spermicide, a cervical cap with spermicide; or having a sterile sexual partner. |
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E.4 | Principal exclusion criteria |
1. Use of any analgesics except the study medication or acetaminophen (paracetamol) at any time during this study. Excluded analgesics include products containing any amount of aspirin (including low dose aspirin for cardioprotection), NSAIDS or COX-2 specific inhibitors. Products containing opioids (including propoxyphene, hydromorphone, hydrocodone, oxycodone, codeine, dihydrocodeine, tramadol, pentazocine, butorphanol, buprenorphine, nalbuphine, levorphanol, methadone, morphine, or fentanyl) are also excluded;
2. Presence or history of peripheral edema within the past 5 years;
3. History of congestive heart failure;
4. Use of chemotherapy agents or history of cancer, other than non-metastatic skin cancer that has been completely excised, within five (5) years prior to the screening visit;
5. History of bacterial or viral infection requiring treatment with antibiotics, antivirals, or anti-retrovirals within 3 months of study;
6. Use of drugs which are P450 3A4 inducers or inhibitors within the past 30 days (e.g. alprazolam, chlorpheniramine, cimetidine, fluoxetine, haloperidol, ketoconazole, itraconazole, erythromycin, clarithromycin, sildenafil, simvastatin, St. John’s Wort;
7. Use of prescribed systemic or topical medications or any dietary aids or foods that are known to modulate drug metabolizing enzymes (e.g. grapefruit juice) within 14 days of dose administration;
8. Difficulty in swallowing oral medications;
9. Subjects with gout, pseudogout, inflammatory arthritis, Paget’s disease of bone, chronic pain syndrome, fibromyalgia, or another major joint disease;
10. 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;
11. Subjects who have had surgery on the affected joint within one year prior to the study and subjects with a prosthesis at the index joint;
12. Use of systemic corticosteroids within 2 months of screening, or intra-articular viscosupplementation within the past 6 months;
13. History of seizure disorder;
14. Use of antidepressants or anticonvulsants for any reason including for chronic pain within 2 months of screening;
15. Serious psychosocial co-morbidities;
16. Cognitive or psychiatric disorders, or daytime use of medications (alcohol, benzodiazepines, barbiturates, muscle relaxants) that could diminish compliance with study procedures, including maintenance of a daily pain and symptom diary and accurate dosing of study medication;
17. Use of anticoagulants (aspirin, warfarin, heparin) within 2 weeks of screening;
18. Use of any medications that will affect pain perception (e.g. tranquilizers, hypnotics);
19. History of drug or alcohol abuse within one year prior to screening;
20. Use of any other investigational drug within 1 month prior to randomization;
21. Active gastrointestinal, renal, hepatic, or coagulant disorder within 1 month prior to randomization;
22. Esophageal or gastroduodenal ulceration within 1 month prior to randomization;
23. Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs), sulfonamides, cyclooxygenase (COX)-2 inhibitors, or carbonic anhydrase inhibitors;
24. History of nasal polyps, bronchospasm, and urticaria;
25. Known allergy or hypersensitivity to sulfa drugs;
26. Family history of significant cardiac disease (i.e. sudden death in first degree relative; myocardial infarction prior to 50 years old);
27. Occult blood in stool (fecal occult blood test).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the change in the sum of the WOMAC OA index at Day 21 vs. Baseline (Day 0). The primary analysis will be via repeated measures using mixed effects ANOVA with baseline and subject as random variables. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |