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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cara Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00877799
First received: April 6, 2009
Last updated: April 23, 2015
Last verified: April 2015
  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 immediately after surgery (Cohort 2).


Condition Intervention Phase
Acute Pain
Drug: CR845
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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:


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

Primary Outcome Measures:
  • Responders on Pain Intensity(PI) and Pain Relief (PR) Composite Endpoint [ Time Frame: 15 and 30 minutes after study drug administration ] [ Designated as safety issue: No ]
    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:
  • Total PCA Morphine Consumption in the 0-16 Hour Period Following Postoperative Study Drug Treatment [ Time Frame: 0 to 16 hours ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Total PCA Morphine Consumption in the 4-8 Hour Period Following Postoperative Study Drug Treatment [ Time Frame: 4 to 8 hours ] [ Designated as safety issue: No ]
  • Total PCA Morphine Consumption in the 8-16 Hour Period Following Postoperative Study Drug Treatment [ Time Frame: 8 to 16 hours ] [ 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: 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)
Drug: CR845
CR845 (0.024 mg/kg) administered the day after surgery (Day 1)
Other Name: Cohort 1: CR845 0.024 mg/kg
Drug: CR845
CR845 (0.008 mg/kg) administered the day after surgery (Day 1)
Other Name: Cohort 1: CR845 0.008 mg/kg
Drug: CR845
CR845 (0.040 mg/kg) administered immediately after surgery (Day 0)
Other Name: Cohort 2: CR845 0.040 mg/kg
Placebo Comparator: 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)
Drug: Placebo
Matched placebo administered the day after surgery (Day 1)
Other Name: Cohort 1: Matched placebo
Drug: Placebo
Matched placebo administered immediately after surgery (Day 0)
Other Name: Cohort 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: 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.
  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: Cara Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT00877799     History of Changes
Other Study ID Numbers: CR845-CLIN2001
Study First Received: April 6, 2009
Results First Received: July 24, 2012
Last Updated: April 23, 2015
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:
Acute Pain
Nervous System Diseases
Neurologic Manifestations
Pain
Signs and Symptoms
Analgesics
Peripheral Nervous System Agents
Central Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2015