Study to Evaluate Analgesic Effect of Intravenous Administration of Kappa Agonist CR845 After Hysterectomy Surgery

Phase 2

Completed

Conditions: Acute Pain

Interventions: Drug: CR845
Drug: Placebo

Registration Number: NCT00877799

Lead Sponsor: Cara Therapeutics, Inc.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 114

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CR845	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)
Placebo	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)

Primary Outcome Measures

Name	Time	Method
Responders on Pain Intensity(PI) and Pain Relief (PR) Composite Endpoint	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 Outcome Measures

Name	Time	Method
Total PCA Morphine Consumption in the 0-16 Hour Period Following Postoperative Study Drug Treatment	0 to 16 hours

Trial Locations

Locations (12): Springhill Medical Center
🇺🇸
Mobile, Alabama, United States
The Woman's Hospital of Texas
🇺🇸
Houston, Texas, United States
Paradise Valley Hospital
🇺🇸
Phoenix, Arizona, United States
Mobile Infirmary Medical Center
🇺🇸
Mobile, Alabama, United States
Saddleback Memorial Hospital
🇺🇸
Laguna Hills, California, United States
Memorial Hermann - Memorial City Medical Center
🇺🇸
Houston, Texas, United States
University of Miami/Jackson Memorial Hospital
🇺🇸
Miami, Florida, United States
Adventist Medical Center
🇺🇸
Glendale, California, United States
Helen Keller Hospital
🇺🇸
Sheffield, Alabama, United States
Palms West Hospital
🇺🇸
Loxahatchee, Florida, United States
Huntington Memorial Hospital
🇺🇸
Pasadena, California, United States
The Ohio State University Medical Center
🇺🇸
Columbus, Ohio, United States