A Study to Compare Levels of Capsaicin After Intra-Articular Injection and Topical Application in Patients With Painful Knee Osteoarthritis

Study Overview
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Brief Summary
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This is a Phase 1b, open-label, two-period, randomized crossover study in adult male and female participants with painful knee osteoarthritis.

Official Title
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A Two-Period Crossover Study to Compare the Systemic Exposure to Trans-Capsaicin and Cis-Capsaicin From an Intra-Articular Injection of CNTX-4975-05 (Trans-capsaicin for Injection) and Topical 8% Capsaicin Patch (Qutenza®) in Subjects With Painful Knee Osteoarthritis

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Drug: CNTX-4975-05
* Drug: Qutenza
* Drug: Lidocaine (without epinephrine)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Body mass index (BMI) between 18.0-35.0 kg/m^2 Subject has moderate to severe painful osteoarthritis in one knee while walking (index knee); contralateral knee may or may not have osteoarthritis, pain should be none to mild in the non-index knee Confirmation of the OA of the index knee: American College of Rheumatology (ACR) diagnostic criteria Subject has intact skin at the location of the dosing sites (patch or injection) Key Exclusion Criteria: Subject has any other form of arthritis, such as, but not limited to, rheumatoid arthritis, psoriatic arthritis, gout, systemic lupus erythematosus, etc. Subject has a dermatological condition that may contraindicate participation, including any compromise in skin integrity at the CNTX-4975-05 injection site or the Qutenza® skin application site, e.g., severe or cystic acne, psoriasis, eczema, atopic dermatitis, active or treated cancer, etc.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CNTX-4975-05 Intra-Articular (IA) Injection<br>Receives IA injection into the most painful OA knee. | Drug: CNTX-4975-05<br>* 1 mg (2mL) IA injection<br>* Other names: trans-capsaicin;Drug: Lidocaine (without epinephrine)<br>* 15 mL IA injection of 2% lidocaine (without epinephrine)<br>|
| Active Comparator: Topical 8% Capsaicin Patch<br>Receives Capsaicin Patch on posterior rib cage. | Drug: Qutenza<br>* 8% topical patch<br>* Other names: cis-capsaicin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Capsaicin Pharmacokinetics - AUC0-t | Single-dose systemic exposure to trans- and cis-capsaicin measured by AUC0-t. | Day 1 (pre-dose to 12 hours post-dose) and Day 8 (pre-dose to 12 hours post-dose) | 
| Capsaicin Pharmacokinetics - AUC0-inf | Single-dose systemic exposure to trans- and cis-capsaicin measured by AUC0-inf. | Day 1 (pre-dose to 12 hours post-dose) and Day 8 (pre-dose to 12 hours post-dose) | 
| Capsaicin Pharmacokinetics - Cmax | Single-dose systemic exposure to trans- and cis-capsaicin measured by Cmax. | Day 1 (pre-dose to 12 hours post-dose) and Day 8 (pre-dose to 12 hours post-dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee Injury and Osteoarthritis Outcome Score (KOOS) Assessment | Change from baseline in KOOS of IA injected knees; 5-point Likert scale: 0 (no problems) to 4 (extreme problems); 5 subscales; each assessed separately | Day 1 (pre-dose) or Day 8 (pre-dose) [cross over trial Qutenza® 8% patch or CNTX-4975-05 intra-articular (IA) knee injection], and Week 8 (follow-up) | 
| Incidence of treatment-emergent adverse events (TEAEs) (safety and tolerability) | Number of participants with TEAEs, which includes laboratory test variables | Day 1 (post-dose), Day 8 (post-dose), and Week 8 (follow-up) | 
| IA knee Lidocaine Systemic Pharmacokinetics - Concentration | System exposure to lidocaine measured by plasma concentration | Day 1 (pre-dose to 3 hours post-dose) or Day 8 (pre-dose to 3 hours post-dose) [Cross over trial Qutenza® 8% patch or CNTX-4975-05 IA knee injection] | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Knee