Clinical trial NCT00877799: Study to Evaluate Analgesic Effect of Intravenous Administration of Kappa Agonist CR845 After Hysterectomy Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Pain
Keywords: pain
acute pain
visceral pain
kappa agonist
opioid analgesics
peripheral nervous system agents
physiological effects of drugs
surgery
hysterectomy
post-operative
post-operative complications
Lead sponsor: Cara Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2009-04-08
Enrollment: 114
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Responders on Pain Intensity(PI) and Pain Relief (PR) Composite Endpoint
timeFrame: 15 and 30 minutes after study drug administration
Secondary outcomes:
measure: Total PCA Morphine Consumption in the 0-16 Hour Period Following Postoperative Study Drug Treatment
timeFrame: 0 to 16 hours
Other outcomes:
measure: Total PCA Morphine Consumption in the 4-8 Hour Period Following Postoperative Study Drug Treatment
timeFrame: 4 to 8 hours
measure: Total PCA Morphine Consumption in the 8-16 Hour Period Following Postoperative Study Drug Treatment
timeFrame: 8 to 16 hours
Locations:
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Mobile
country: United States
facility: Springhill Medical Center
state: Alabama
city: Sheffield
country: United States
facility: Helen Keller Hospital
state: Alabama
city: Phoenix
country: United States
facility: Paradise Valley Hospital
state: Arizona
city: Glendale
country: United States
facility: Adventist Medical Center
state: California
city: Laguna Hills
country: United States
facility: Saddleback Memorial Hospital
state: California
city: Pasadena
country: United States
facility: Huntington Memorial Hospital
state: California
city: Loxahatchee
country: United States
facility: Palms West Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami/Jackson Memorial Hospital
state: Florida
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Houston
country: United States
facility: Memorial Hermann - Memorial City Medical Center
state: Texas
city: Houston
country: United States
facility: The Woman's Hospital of Texas
state: Texas
Study officials:
affiliation: Cara Therapeutics, Inc.
name: Frédérique Menzaghi, Ph.D.
role: STUDY_DIRECTOR
References: