A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study to Evaluate the Analgesic Efficacy and Safety of Intravenous CR845 During the Post-Operative Period in Subjects Undergoing Laparoscopic-Assisted Hysterectomy
Overview
- Phase
- Phase 2
- Intervention
- CR845
- Conditions
- Acute Pain
- Sponsor
- Cara Therapeutics, Inc.
- Enrollment
- 114
- Locations
- 12
- Primary Endpoint
- Responders on Pain Intensity(PI) and Pain Relief (PR) Composite Endpoint
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The purpose of this study is to determine the effectiveness and safety of single intravenous doses of the kappa opioid agonist CR845 in relieving pain in patients following laparoscopic-assisted hysterectomy surgery. The study protocol was divided into two parts with subjects either dosed with study drug the day following surgery (Cohort 1), or immediately after surgery (Cohort 2).
Detailed Description
Currently, the most widely used drugs to treat pain after surgery are opiates, such as morphine. Morphine works mainly by activating one of several types of opiate receptors that control some of our pain sensation - the so-called mu opiate receptors. These receptors are located in many areas of the brain and also outside of the brain. By activating these receptors, morphine provides significant pain relief, but also causes side effects that limit its use. Some of these side effects include: respiratory depression or arrest (slowed or stopped breathing), sedation (a state of calmness or extreme relaxation), euphoria (an exaggerated feeling of physical and mental well-being), constipation, nausea, vomiting, and drug addiction. In order to avoid the side effects of morphine and other mu opiates, the present experimental drug CR845 was designed to work at a different type of opiate receptor - called kappa - that can also provide pain relief, by acting on sensory nerves outside the brain. CR845 was designed to penetrate the brain much less than other opiate drugs, which should result in pain relief similar to that of morphine, but with fewer side effects. Because CR845 activates kappa receptors instead of mu receptors, the side effects are different than with a morphine-type drug. In particular, kappa opiates, such as CR845, do not cause respiratory depression or arrest, euphoria, constipation, drug tolerance, physical drug dependence or drug addiction. For these reasons, CR845 may present a distinct advantage over other opiates that are currently used for pain relief and post-operative pain in particular.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The patients will have an elective laparoscopic-assisted hysterectomy under general anesthesia.
- •The patient's preoperative health is graded as the American Society of Anesthesiologists (ASA) risk class of I to III
Exclusion Criteria
- •The patient has a history of known allergies to opioids
- •The patient is currently taking opioid analgesics chronically or took opioid analgesics on at least 4 days during the week before surgery.
- •Patients having additional procedures (such as those involving the bladder) at the same time as the laparoscopic-assisted hysterectomy.
- •Patients taking short-acting oral analgesics (eg, acetaminophen, aspirin, ibuprofen, ketorolac) within 6 hours before administration of study drug; long-acting nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, naproxen, oxaprozin, piroxicam, celecoxib) within 3 days before administration of study drug; systemic steroids within 72 hours before administration of study drug; or any opioid analgesics or tramadol daily for greater than 10 days of the last 30 days before administration of study drug.
- •Patients taking the following herbal agents or nutraceuticals within 7 days prior to beginning of the study: chaparral, comfrey, germander, gin bu huan, kava, pennyroyal, skullcap, St. John's wort, or valerian.
- •Patients with clinically significant cardiovascular disease, or cardiac arrhythmias, or significant major risk factors for cardiovascular disease such as poorly controlled hypertension, poorly controlled hypercholesterolemia, poorly controlled diabetes mellitus or serious medical conditions, such as cancer.
- •Patient has a history of hepatitis B or C or HIV infection with positive hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (HCV) antibody test.
Arms & Interventions
CR845
CR845 administered as a single 15-min i.v. infusion at doses of 0.008 or 0.024 mg/kg on the day after surgery (Cohort 1), or at a dose of 0.040 mg/kg immediately after surgery (Cohort 2)
Intervention: CR845
Placebo
Matched placebo administered as a single 15-min i.v. infusion on the day after surgery (Cohort 1), or the immediately after surgery (Cohort 2)
Intervention: Placebo
Outcomes
Primary Outcomes
Responders on Pain Intensity(PI) and Pain Relief (PR) Composite Endpoint
Time Frame: 15 and 30 minutes after study drug administration
The primary efficacy endpoint was the percentage of treatment responders compared to placebo. A responder was defined as a subject who had at least a 40% reduction in their pain intensity score and a pain relief score of "some," "a lot," or "complete" at 15 and 30 min following the start of the study drug infusion.
Secondary Outcomes
- Total PCA Morphine Consumption in the 0-16 Hour Period Following Postoperative Study Drug Treatment(0 to 16 hours)