Non-Opioid Pain Therapy Derived from Chili Plant Shows Promise for Knee Osteoarthritis Pain

Non-Opioid Pain Therapy Derived from Chili Plant Shows Promise for Knee Osteoarthritis Pain

By Staff

People with knee osteoarthritis (OA) pain that are participating in a clinical trial of CNTX-4975 are getting some promising results so far.

In the randomized, double-blind, placebo-controlled, multicenter TRIUMPH study, CNTX-4975, met its primary endpoint of a reduction in pain with walking through 12 weeks with high statistical significance and demonstrated a duration of effect of at least 24 weeks after a single dose.  At the 1.0 mg dose, two-thirds of patients achieved 50 percent or greater reduction in pain and nearly one-quarter of patients achieved a 90 percent or greater reduction in pain

“As our population ages, chronic osteoarthritis pain is an important and growing problem. Short of joint replacement which carries risks associated with any surgery, there are insufficient options and severe osteoarthritis pain is one of the most common reasons patients take opioids,” said Nathaniel Katz M.D., M.S., adjunct associate professor of anesthesia at Tufts University School of Medicine.

“It is critical to develop effective non-opioid therapies that can avoid the abuse and addiction issues associated with opioid treatments and CNTX-4975 represents an important new approach for pain relief for patients. The results seen in this clinical trial suggest that the medicine warrants further clinical investigation,” Dr. Katz added.

“We are very encouraged by the extent and duration of pain relief treatment seen with CNTX-4975, particularly at the 1.0 mg dose. We look forward to discussing these results with the FDA and initiating Phase 3 development of CNTX-4975 next year,” said Randall M. Stevens, M.D., chief medical officer for Centrexion Therapeutics, the manufacturer of the therapy.

CNTX-4975 is a synthetic form of trans-capsaicin (a medicine traditionally derived from the chili plant.  It’s designed to be injected directly into the site of pain to provide rapid onset, large reduction and long duration of relief from moderate to severe pain without affecting touch sensibility or position sense.

It works by selectively targeting the capsaicin receptor (TRPV1) to rapidly inactivate only the local pain fibers transmitting signals to the brain.  This approach provides pain relief that can last for months until the ends of the local pain fibers regenerate, while leaving the rest of the nerve fiber functioning as normal, and without the risks of toxicities of NSAIDs and injected steroids or the side effects, including abuse and addiction, associated with opioid treatments.

The dose-ranging Phase 2b study evaluated the safety and efficacy of CNTX-4975 in 175 patients with chronic moderate to severe knee OA pain over 24 weeks. Patients were randomized to receive either a single injection into the knee of CNTX-4975 0.5 mg (n=34), CNTX-4975 1.0 mg (n=71) or placebo (n=70). The primary endpoint was pain with walking (WOMAC [Western Ontario and McMaster Universities Arthritis Index] A1) at Week 12.

Secondary outcome measures included knee joint stiffness and function (both assessed by WOMAC B and WOMAC C, respectively), patient global impression of change (PGIC), responder analysis (the proportion of patients improved by percent from baseline pain), and safety and tolerability. Additional follow-up to 24 weeks was conducted to assess the duration of response from a single injection.

Results through 12 weeks showed that both doses of CNTX-4975 were significantly more effective than placebo in the primary endpoint of pain with walking.  For the 1.0 mg dose:

  • Both weekly pain and daily pain measures were highly statistically significant (p<0.001)
  • Twenty-two percent of patients achieved a 90 percent or greater reduction in pain and 67 percent of patients achieved 50 percent or greater reduction in pain
  • CNTX-4975 was significantly more effective than placebo in the secondary outcome measures of stiffness, function and PGIC at every time point
  • The onset of pain reduction occurred within days and reached statistical significance at Week 1
  • Maximum effect was seen at Week 5 and a stable, statistically significant response at every time point was observed through Week 12

Through 24 weeks with the 1.0 mg dose, the study met the endpoint of duration of response with statistical significance with a single dose of CNTX-4975 compared to placebo.

Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 14 million people in the United States.  It occurs when the protective cartilage on the ends of the bones wears down over time, and the bone around the joints harden and form edges. These changes cause pain, swelling and problems moving the joint. OA also causes an inflammatory process to occur in the affected joint, further damaging the cartilage.

Subscribe to our blog via email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

Authored by: Staff

newest oldest
Notify of

Kathy before all this research people treated themselves with whatever worked!


I currently use cbd oil with moderate relief but not for long as they are in the process of a total ban on cbd oil!

Jean Price

Pain itself ALSO causes MORE INFLAMMATORY responses, delaying healing AND damaging tissue…along with lives! So sadly, during our current status of less than effective pain treatment…or even NO treatment whatsoever.., there is very likely much damage being done to an untold number of patients…those with persistent, daily pain in various areas of their bodies! Why no one is thinking about this is beyond me! When I see a study like this and realize how long it will be before these treatments are available, I shudder to think of all the pain damage happening RIGHT NOW. And the lives that are being damaged too! I’m all for research, yet what happens to those lost between the cracks of no care and new care methods!?! And why does no one in the medical field seem to be up in arms about this?! PITIFUL!!

Kathy C

This will be a real Profit generator for Knee Pain. There is money to be made here so this will be Marketed to it’s full potential. The Patient will have to keep coming back for these Profitable procedures. They will make money on the Inject able, and the procedure. Many Insurance companies cover this for now, so this can be very profitable. A 1400.00 procedure every 12 weeks, KaChing! This is not really a breakthrough, there are a lot of substances that when injected into an Arthritic joint aggravate it enough for temporary relief. The opiate Hysteria is a great marketing tool, since even amputating the affected limb appears to be better than risking the horrors of Addiction.
I wonder what people did before they had all of this big Research.


I am happy to see that there is ongoing research for a safe way to control pain especially chronic pain. If the chili plant has properties that help with osteoarthritis pain, that’s great. It seems that CBD less the THC from the marijuana plant has some pretty amazing testomonials from the community for its pain relieving properties along with other great properties. It’s O.K. to research the chili plant or any other plant for propertes that have been missed or neglected. For myself, I am gonna continue to research CBD. I, along with millions of others need help now since opioid treatment is coming under so much attention. More pqwer to help that is non-addictive, can’t overdose on, and available…….now. .


The numbers look good. I wonder if it would work on all types of osteoarthritis pain and if being synthetic it would make my stomach burn like the current forms of capsaicin do?