Study to Evaluate Analgesic Effect of Intravenous Administration of Kappa Agonist CR845 After Hysterectomy Surgery - Full Text View

Purpose

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 the day of surgery (Cohort 2).

Condition	Intervention	Phase
Acute Pain Post-operative Pain	Drug: CR845	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Hysterectomy

U.S. FDA Resources

Further study details as provided by Cara Therapeutics, Inc.:

Primary Outcome Measures:

Analgesic efficacy measured by patient's self reported pain level at rest after surgery (after single dose administration). [ Time Frame: After single dose administered , for Cohort 1: 24 hours post-surgery and 12 hour period of observation and for Cohort 2: within 3 hours post-surgery, 8 hour period of observation ] [ Designated as safety issue: No ]
The analgesic efficacy was measured in Cohort 1 by patient's self reported pain level at rest using a visual analog scale on the first day after surgery (after single dose administration). In Cohort 2 the analgesic efficacy was measured by patient's self reported pain level at rest using a numerical rating scale the day of surgery (after single dose administration).

Secondary Outcome Measures:

Time to onset of analgesic efficacy [ Time Frame: Cohort 1: 24 hours post-surgery, 12 hour period of observation after single dose is administered. Cohort 2: within 3 hours post-surgery, over 8 hour period of observation after single dose administered ] [ Designated as safety issue: No ]
Time specific and total level of pain relief [ Time Frame: Cohort 1: 24 hours post-surgery, 12 hour period of observation after single dose is administered. Cohort 2: within 3 hours post-surgery, over 8 hour period of observation after single dose administered ] [ Designated as safety issue: No ]
Duration of analgesia [ Time Frame: Cohort 1: 24 hours post-surgery, 12 hour period of observation after single dose is administered. Cohort 2: within 3 hours post-surgery, over 8 hour period of observation after single dose administered ] [ Designated as safety issue: No ]
Time specific pain intensity difference from baseline and total level of pain relief [ Time Frame: Cohort 1: 24 hours post-surgery, 12 hour period of observation after single dose is administered. Cohort 2: within 3 hours post-surgery, over 8 hour period of observation after single dose administered ] [ Designated as safety issue: No ]
Time and requirement for rescue medication including survival curve of patients requesting rescue medication [ Time Frame: Cohort 1: 24 hours post-surgery, 12 hour period of observation after single dose is administered. Cohort 2: within 3 hours post-surgery, over 8 hour period of observation after single dose administered ] [ Designated as safety issue: No ]
Patient satisfaction with study medication with the patient Global evaluation scale [ Time Frame: Cohort 1: at 12 hours post-dose or prior to rescue medication. Cohort 2: at 8 hours post-dose or prior to rescue medication ] [ Designated as safety issue: No ]
Vital signs, clinical laboratory parameters, ECG [ Time Frame: For both Cohorts 1 and 2, pre and post-dose until hospital discharge and 7-10 days after surgical procedure ] [ Designated as safety issue: Yes ]
Incidence of adverse events (AEs) [ Time Frame: For both Cohorts 1 and 2, until 7-10 days after the surgical procedure ] [ Designated as safety issue: Yes ]
Sedation as measured by Ramsay sedation scale [ Time Frame: Cohort 1: within 12 hour period of observation after single dose is administered. Cohort 2: within 8 hour period of observation after single dose is administered. ] [ Designated as safety issue: No ]
Anti-inflammatory effects (measured by quantification of serum TNF alpha and serum IL-6 [ Time Frame: Within 12 hour period of observation after single dose is administered. This exploratory endpoint was not included in Cohort 2. ] [ Designated as safety issue: No ]


Enrollment:	114
Study Start Date:	March 2009
Study Completion Date:	January 2010
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Cohort 1 - CR845 - I.V. 0.008 mg/kg single dose 24 hours post-surgery	Drug: CR845 Experimental: CR845 0.008 mg/kg I.V. (in the vein) 24 hours after surgery, infusion for 15 minutes Experimental: CR845 0.024 mg/kg I.V. (in the vein) 24 hours after surgery, infusion for 15 minutes Placebo Comparator: Matched Placebo Experimental: CR845 0.040 mg/kg I.V. (in the vein) within 3 hours after surgery, infusion for 15 minutes Placebo Comparator 2: Matched Placebo
Experimental: 2 Cohort 1 - CR845 - I.V. 0.024 mg/kg single dose 24 hours post-surgery	Drug: CR845 Experimental: CR845 0.008 mg/kg I.V. (in the vein) 24 hours after surgery, infusion for 15 minutes Experimental: CR845 0.024 mg/kg I.V. (in the vein) 24 hours after surgery, infusion for 15 minutes Placebo Comparator: Matched Placebo Experimental: CR845 0.040 mg/kg I.V. (in the vein) within 3 hours after surgery, infusion for 15 minutes Placebo Comparator 2: Matched Placebo
Placebo Comparator: 3 Cohort 1 - Matched Placebo single I.V. within 24 hours post-surgery	Drug: CR845 Experimental: CR845 0.008 mg/kg I.V. (in the vein) 24 hours after surgery, infusion for 15 minutes Experimental: CR845 0.024 mg/kg I.V. (in the vein) 24 hours after surgery, infusion for 15 minutes Placebo Comparator: Matched Placebo Experimental: CR845 0.040 mg/kg I.V. (in the vein) within 3 hours after surgery, infusion for 15 minutes Placebo Comparator 2: Matched Placebo
Experimental: 4 Cohort 2 - CR845 - I.V. 0.040 mg/kg single dose within 3 hours post-surgery	Drug: CR845 Experimental: CR845 0.008 mg/kg I.V. (in the vein) 24 hours after surgery, infusion for 15 minutes Experimental: CR845 0.024 mg/kg I.V. (in the vein) 24 hours after surgery, infusion for 15 minutes Placebo Comparator: Matched Placebo Experimental: CR845 0.040 mg/kg I.V. (in the vein) within 3 hours after surgery, infusion for 15 minutes Placebo Comparator 2: Matched Placebo
Placebo Comparator: 5 Cohort 2 - Placebo Comparator 2 - Matched Placebo single I.V. within 3 hours post-surgery	Drug: CR845 Experimental: CR845 0.008 mg/kg I.V. (in the vein) 24 hours after surgery, infusion for 15 minutes Experimental: CR845 0.024 mg/kg I.V. (in the vein) 24 hours after surgery, infusion for 15 minutes Placebo Comparator: Matched Placebo Experimental: CR845 0.040 mg/kg I.V. (in the vein) within 3 hours after surgery, infusion for 15 minutes Placebo Comparator 2: Matched Placebo

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


Ages Eligible for Study:	21 Years to 60 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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: chapparal, 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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00877799

Locations


United States, Alabama
Mobile Infirmary Medical Center
Mobile, Alabama, United States, 36607
Springhill Medical Center
Mobile, Alabama, United States, 36608
Helen Keller Hospital
Sheffield, Alabama, United States, 35660
United States, Arizona
Paradise Valley Hospital
Phoenix, Arizona, United States, 85032
United States, California
Adventist Medical Center
Glendale, California, United States, 91206
Saddleback Memorial Hospital
Laguna Hills, California, United States, 92653
Huntington Memorial Hospital
Pasadena, California, United States, 91105
United States, Florida
Palms West Hospital
Loxahatchee, Florida, United States, 33472
University of Miami/Jackson Memorial Hospital
Miami, Florida, United States, 33136
United States, Ohio
The Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Texas
Memorial Hermann - Memorial City Medical Center
Houston, Texas, United States, 77024
The Woman's Hospital of Texas
Houston, Texas, United States, 77054

Sponsors and Collaborators

Cara Therapeutics, Inc.

Investigators


Study Director:	Frédérique Menzaghi, Ph.D.	Cara Therapeutics, Inc.

More Information

No publications provided


Responsible Party:	Frédérique Menzaghi, Ph.D., Vice President, Research & Development, Cara Therapeutics, Inc.
ClinicalTrials.gov Identifier:	NCT00877799 History of Changes
Other Study ID Numbers:	CR845-CLIN2001
Study First Received:	April 6, 2009
Last Updated:	April 16, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Cara Therapeutics, Inc.:


pain acute pain visceral pain kappa agonist opioid analgesics peripheral nervous system agents	physiological effects of drugs surgery hysterectomy post-operative post-operative complications

Additional relevant MeSH terms:


Analgesics Central Nervous System Agents Peripheral Nervous System Agents Pharmacologic Actions	Physiological Effects of Drugs Sensory System Agents Therapeutic Uses

ClinicalTrials.gov processed this record on March 01, 2015