Phase 2
Completed N=476
A Study Evaluating Pain Relief and Safety of Orally Administered CR845 in Patients With Osteoarthritis of Hip or Knee
Osteoarthritis, Hip · Osteoarthritis, Knee · Arthritis · Joint Diseases
Source: ClinicalTrials.gov NCT02944448 ↗
Enrolled (actual)
476
Serious AEs
2.1%
Results posted
Oct 2020
Primary outcomePrimary: Change From Baseline at Week 8 With Respect to the Weekly Mean of the Daily 24-hour Pain Intensity for the Index Joint as Measured by the Numeric Rating Scale (NRS). — -2.3; -2.4 score on a scale — p=0.7093
Summary
The study schedule consists of a Screening Period (up to 14 days), a blinded 4- week Titration-to-Effect Period with weekly visits, a blinded 4-week Maintenance Treatment Period at the optimal dose level determined for each patient, and a 1-week Follow-up Period.
Eligible patients will be randomized to receive either CR845 or placebo in a 2:1 ratio. Every patient will be started on a 1-mg dose of CR845 or matching placebo. During the post-randomization Titration-to-Effect period, the dose of study drug may be increased to 2.5 mg or 5 mg in a double-blind fashion. Patients may know their dose is being changed but will not know whether they were randomization to active study drug or placebo. Approximately 330 patients will be enrolled in this study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline at Week 8 With Respect to the Weekly Mean of the Daily 24-hour Pain Intensity for the Index Joint as Measured by the Numeric Rating Scale (NRS). |
-2.3; -2.4 | 0.7093 |
| SECONDARY Change From Baseline in the Western Ontario & McMaster Osteoarthritis (WOMAC) Index Total Score at Week 8 |
-62.4; -59.7 | 0.6007 |
| SECONDARY Change From Baseline in the WOMAC Pain Intensity Sub-scale Score at Week 8 |
-13.5; -12.7 | 0.4563 |
| SECONDARY Change From Baseline in the WOMAC Stiffness Sub-scale Score at Week 8 |
-5.7; -5.6 | 0.8693 |
| SECONDARY Change From Baseline in the WOMAC Function Sub-scale Score at Week 8 |
-43.1; -41.5 | 0.6516 |
| SECONDARY Proportion of Patients With at Least 30% Improvement From Baseline in the Weekly Mean Pain Intensity at Week 8 |
41.5; 50.6 | 0.1033 |
| SECONDARY Proportion of Patients With at Least 50% Improvement From Baseline in the Weekly Mean Pain Intensity at Week 8 |
25.6; 31.3 | 0.2831 |
| SECONDARY Proportion of Patients Whose OA Pain Was "Very Much Improved" or "Much Improved" as Indicated by Patient Global Impression of Change (PGIC) Score at Week 8 |
44.3; 40.0 | 0.1959 |
| SECONDARY Average Daily Number of Acetaminophen Tablets Used During Entire Study |
0.5; 0.4 | 0.2858 |
| SECONDARY Proportion of Patients Withdrawing From Treatment Due to Lack of Analgesic Efficacy |
2.5; 3.1 | 0.8002 |
Eligibility Criteria
Inclusion Criteria
- Voluntarily provides written informed consent to participate in the study prior to any study procedures.
- Is able to speak, read, and communicate clearly in English or Spanish; is able to understand the study procedures.
- Male or female ≥ 25 years of age.
- Body mass index (BMI) ≤ 40 kg/m2.
- Has OA of the hip or knee according to American College of Rheumatology (ACR) criteria.
- Reports an average pain intensity level ≥ 5 in the index joint at Screening on a 0-10 NRS scale.
- Is either opioid-naïve (defined as taking 40 mg of morphine equivalent.
- Uses antipsychotics, antiepileptics, sedatives, hypnotics, or antianxiety agents, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants with a dose change 20 mm Hg or a decrease in diastolic blood pressure by 10 mm Hg together with an increase in heart rate of > 30 beats per minute when transitioning from supine to standing measurements.
- Has a medical condition (e.g., a cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine [adrenal hyperplasia], immunologic, dermatologic, neurologic, oncologic, or psychiatric) or a significant laboratory abnormality that, in the Investigator's opinion, would jeopardize the safety of the patient or is likely to confound the study measurements.
- Has had any gastric bypass surgery (for weight loss).
- Has a corrected QT interval of >450 msec in males, >470 msec in females, or clinically significant abnormality on screening ECG.
- Has a serum sodium level > 143 mmol/L at Screening.
- Has impaired renal function indicated by serum creatinine > 2 × the reference upper limit of normal (ULN).
- Has a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × the reference ULN, or total bilirubin > 2 × the ULN at Screening.
- Has, in the opinion of the Investigator, any clinical signs of dehydration or hypovolemia (e.g., symptomatic hypotension) or associated laboratory abnormalities (e.g., elevated hematocrit or elevated blood urea nitrogen [BUN] > 1.5 × the reference ULN) at Screening.
- Has taken opioid or non-opioid pain medication (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs] such as naproxen or cyclooxygenase-2 inhibitors) within 5 days prior to study drug administration. Acetaminophen use is allowed. (Section 8.8)
- Has received another investigational drug within 30 days prior to Baseline or has planned to participate in another clinical trial while enrolled in this study.
Data sourced from ClinicalTrials.gov (NCT02944448). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.