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

Primary Purpose

Acute Pain

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CR845
CR845
CR845
Placebo
Placebo
Sponsored by
Cara Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Pain focused on measuring pain, acute pain, visceral pain, kappa agonist, opioid analgesics, peripheral nervous system agents, physiological effects of drugs, surgery, hysterectomy, post-operative, post-operative complications

Eligibility Criteria

21 Years - 60 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Mobile Infirmary Medical Center
  • Springhill Medical Center
  • Helen Keller Hospital
  • Paradise Valley Hospital
  • Adventist Medical Center
  • Saddleback Memorial Hospital
  • Huntington Memorial Hospital
  • Palms West Hospital
  • University of Miami/Jackson Memorial Hospital
  • The Ohio State University Medical Center
  • Memorial Hermann - Memorial City Medical Center
  • The Woman's Hospital of Texas

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

CR845

Placebo

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

Responders on Pain Intensity(PI) and Pain Relief (PR) Composite Endpoint
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

Full Information

First Posted
April 6, 2009
Last Updated
April 23, 2015
Sponsor
Cara Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00877799
Brief Title
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

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
January 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cara Therapeutics, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
114 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CR845
Arm Type
Experimental
Arm Description
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)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
CR845
Other Intervention Name(s)
Cohort 1: CR845 0.024 mg/kg
Intervention Description
CR845 (0.024 mg/kg) administered the day after surgery (Day 1)
Intervention Type
Drug
Intervention Name(s)
CR845
Other Intervention Name(s)
Cohort 1: CR845 0.008 mg/kg
Intervention Description
CR845 (0.008 mg/kg) administered the day after surgery (Day 1)
Intervention Type
Drug
Intervention Name(s)
CR845
Other Intervention Name(s)
Cohort 2: CR845 0.040 mg/kg
Intervention Description
CR845 (0.040 mg/kg) administered immediately after surgery (Day 0)
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Cohort 1: Matched placebo
Intervention Description
Matched placebo administered the day after surgery (Day 1)
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Cohort 2: Matched placebo
Intervention Description
Matched placebo administered immediately after surgery (Day 0)
Primary Outcome Measure Information:
Title
Responders on Pain Intensity(PI) and Pain Relief (PR) Composite Endpoint
Description
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.
Time Frame
15 and 30 minutes after study drug administration
Secondary Outcome Measure Information:
Title
Total PCA Morphine Consumption in the 0-16 Hour Period Following Postoperative Study Drug Treatment
Time Frame
0 to 16 hours
Other Pre-specified Outcome Measures:
Title
Total PCA Morphine Consumption in the 4-8 Hour Period Following Postoperative Study Drug Treatment
Time Frame
4 to 8 hours
Title
Total PCA Morphine Consumption in the 8-16 Hour Period Following Postoperative Study Drug Treatment
Time Frame
8 to 16 hours

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frédérique Menzaghi, Ph.D.
Organizational Affiliation
Cara Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Mobile Infirmary Medical Center
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36607
Country
United States
Facility Name
Springhill Medical Center
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36608
Country
United States
Facility Name
Helen Keller Hospital
City
Sheffield
State/Province
Alabama
ZIP/Postal Code
35660
Country
United States
Facility Name
Paradise Valley Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85032
Country
United States
Facility Name
Adventist Medical Center
City
Glendale
State/Province
California
ZIP/Postal Code
91206
Country
United States
Facility Name
Saddleback Memorial Hospital
City
Laguna Hills
State/Province
California
ZIP/Postal Code
92653
Country
United States
Facility Name
Huntington Memorial Hospital
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
Palms West Hospital
City
Loxahatchee
State/Province
Florida
ZIP/Postal Code
33472
Country
United States
Facility Name
University of Miami/Jackson Memorial Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
The Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Memorial Hermann - Memorial City Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
Facility Name
The Woman's Hospital of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77054
Country
United States

12. IPD Sharing Statement

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

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