The Effect of Injection Site Cooling on Pain Experienced After the Administration of CNTX-4975-05 Into the Knee

Study Overview
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Brief Summary
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A clinical study to measure the effects of injection-site cooling on pain experienced after knee injections of capsaicin in healthy subjects and in patients with knee osteoarthritis.

Official Title
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A Phase 1b Study to Characterize the Effect of Injection Site Cooling on Pain Experienced After CNTX-4975-05 (Trans-capsaicin) Intra-articular and Capsaicin Intradermal Injections in Healthy Volunteers and Subjects With Bilateral Painful Knee Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Other: Ice Pack and Cooling Device
* Drug: CNTX-4975-05 (trans-capsaicin)
* Drug: CNTX-4975-05 (trans-capsaicin)
* Drug: CNTX-4975-05 (trans-capsaicin)
* Drug: Capsaicin


Participation Criteria
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Eligibility Criteria
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Cohort 1 Key Inclusion Criteria: Subject is aged between 18 and 45 years, inclusive. Subjects Body Mass Index (BMI) is between 18 and 32 kg/m^2, inclusive and subject's weight is greater than or equal to 50 kg. Subjects must be in good health, in the opinion of the Investigator, as determined by a medical history, physical examination, clinical laboratory tests, vital signs and 12 lead electrocardiogram (ECG). Cohort 1 Key Exclusion Criteria: Subject has had a clinically significant illness that has not completely resolved in the four weeks before screening. Subject has a history of neurological disorder which may impact the perception of pain or impairs the subject's ability to fully participate in the trial. Cohorts 2-4 Key Inclusion Criteria: Subject is aged between 45 and 75 years, inclusive. Subject's BMI is between 18 and 32 kg/m^2, inclusive and subject's weight is greater than or equal to 50 kg. Subject has a diagnosis of bilateral moderate to severe painful knee OA (subjects will be required to have a score on Pain with walking in the previous 24 hours, of 4 to 9, inclusive NPRS 0-10). The condition must be chronic with a history of painful arthritis for at least 3 months prior to entry in the study. Cohorts 2-4 Key Exclusion Criteria: Subject has had a clinically significant illness, other than osteoarthritis, that has not completely resolved in the four weeks before screening. Subject has a history of neurological disorder which may impact the perception of pain or impairs the subject's ability to fully participate in the trial. Subject has used analgesic medications in the 2 days prior to dosing, except for paracetamol, as needed. Subject has used topical medications applied to the knee for OA pain (including capsaicin, lidocaine, prescription or OTC medications) from 90 days prior to screening through to dosing. Subject has been injected with corticosteroids in the knee 90 days prior to screening through to dosing. Subject currently uses opioids for any condition other than OA knee pain (maximum dose 15 mg hydrocodone, or equivalent, per day prescribed by a physician).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>A comparison of two cooling methodologies in healthy volunteers after single intra-articular (IA) injection (15 mL) of 2% lidocaine (without epinephrine). | Other: Ice Pack and Cooling Device<br>* A comparison of two cooling methodologies in healthy volunteers after single intra-articular (IA) injection (15 mL) of 2% lidocaine (without epinephrine).<br>Drug: Capsaicin<br>* Four intradermal injections of capsaicin, two on each forearm.<br>|
| Experimental: Cohort 2<br>Controlled cooling wrap versus ice pack cooling. | Drug: CNTX-4975-05 (trans-capsaicin)<br>* Controlled cooling wrap vs ice pack cooling after single IA injection of 1 mg CNTX-4975-05 in each arm after single IA (15 mL) injection of 2% lidocaine (without epinephrine).<br>Drug: Capsaicin<br>* Four intradermal injections of capsaicin, two on each forearm.<br>|
| Experimental: Cohort 3<br>Controlled cooling parameters will be determined after evaluation of data from prior cohorts. | Drug: CNTX-4975-05 (trans-capsaicin)<br>* Controlled cooling parameters will be determined after evaluation of data from prior Cohort(s) after single IA injection (15 mL) of 2% lidocaine (without epinephrine) and single IA injection of 1 mg CNTX-4975-05.<br>Drug: Capsaicin<br>* Four intradermal injections of capsaicin, two on each forearm.<br>|
| Experimental: Cohort 4<br>Controlled cooling with knee device versus no cooling (determined after evaluation of data from previous cohorts). | Drug: CNTX-4975-05 (trans-capsaicin)<br>* Controlled cooling with knee device vs no cooling (determined after evaluation of data from previous cohorts) after single IA injection (15 mL) of 2% lidocaine (without epinephrine) and single IA injection of 1 mg CNTX-4975-05.<br>Drug: Capsaicin<br>* Four intradermal injections of capsaicin, two on each forearm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical Pain Rating Scale (NPRS): Injection-site Pain | Cohorts 2-4: Change in injection-site pain following intra-articular (IA) administration of CNTX-4975-05 (trans-capsaicin) scored using NPRS on a scale of 0 to 10 with 0 corresponding to no pain and 10 corresponding to the worst pain imaginable. | Days 1 and 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IA Temperature | Cohorts 1-4: IA temperature measurements. | Days 1 and 7 | 
| Numerical Pain Rating Scale (NPRS): Procedural Pain | Cohort 1: Procedural pain following single intra-articular (IA) injection (15 mL) of 2% lidocaine (without epinephrine) using NPRS on a scale of 0 to 10 with 0 corresponding to no pain and 10 corresponding to the worst pain imaginable. | Days 1 and 7 | 
| Numerical Pain Rating Scale (NPRS): Procedural Pain | Cohorts 2-4: Procedural pain following intradermal (ID) administration of the challenge agent capsaicin as a function of temperature scored using NPRS on a scale of 0 to 10 with 0 corresponding to no pain and 10 corresponding to the worst pain imaginable. | Days 1 and 7 | 
| Numerical Pain Rating Scale (NPRS): Pain with Walking | Cohorts 2-4: Average pain with walking over the past 24 hours scored using NPRS on a scale of 0 to 10 with 0 corresponding to no pain and 10 corresponding to the worst pain imaginable. | Screening through Day 42 | 
| Knee Injury and Osteoarthritis Outcome Score (KOOS) | Cohorts 2-4: Calculation of KOOS for each painful osteoarthritis knee on a scale of 0 to 100 with 0 representing extreme problems and 100 representing no problems. | Screening through Day 42 | 
| Patient Global Impression of Change (PGIC) | Cohorts 2-4: Change in knee pain for each painful osteoarthritis knee scored using PGIC on a scale of 1 to 7 with 1 representing very much improved and 7 representing very much worse. | Screening through Day 42 | 
| Numerical Pain Rating Scale (NPRS): Thermal Pain | Cohorts 1-4: Thermal pain approximately two weeks following intradermal (ID) administration of the challenge agent capsaicin scored using NPRS on a scale of 0 to 10 with 0 corresponding to no pain and 10 corresponding to the worst pain imaginable. | Between Days 28 and 35 inclusive; and Day 42 | 

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