Study to Evaluate Analgesic Effect of IV Administration of Kappa Agonist CR845 For Hysterectomy Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cara Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01361568
First received: May 25, 2011
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

The primary purpose of this study is to determine if CR845 is effective in treating the pain associated with a laparoscopic hysterectomy.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-Center, Double-Randomized, Double Blind, Placebo Controlled Study to Evaluate the Analgesic Efficacy and Safety of Intravenous CR845 Dosed Preoperatively and Postoperatively in Patients Undergoing a Laparoscopic Hysterectomy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Total Morphine Consumption in the First 24 Hours Following Postoperative Study Drug Treatment [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Summed Pain Intensity Difference From 0-24 Hours (SPID 0-24) Following Postoperative Study Drug Treatment Using Last Observation Carried Forward (LOCF) [ Time Frame: 0 to 24 hours ] [ Designated as safety issue: No ]

    Patients reported their pain intensity using a visual analogue scale (VAS) from 0 to 100 mm, where 0 mm represented "No Pain" and 100 mm represented the "Worst Pain You Can Imagine". SPID 0-24 represents the cumulative time-weighted sum of the pain intensity difference (PID) scores between each assessment timepoint following the postoperative administration of study drug (i.e. 0 to 15 min, 15 to 30 min, etc.) over 24 hours. Pain intensity assessments were measured at baseline (entry pain score), then at 15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, 720, 960, and 1440 minutes after the start of the infusion of study drug following surgery.

    Negative SPID values represent a decrease in pain intensity (i.e. lower values indicate a greater reduction in pain).


  • Morphine Consumption Following Postoperative Study Drug Treatment in the 2-24 Hour Period After Recovery in the Post-Anesthesia Care Unit (Post-PACU) [ Time Frame: 2 to 24 hours (post-PACU) ] [ Designated as safety issue: No ]
  • Total Pain Relief Within the First 2 Hours (TOTPAR 0-2) Following Postoperative Study Drug Treatment Using LOCF [ Time Frame: 0 to 2 hours ] [ Designated as safety issue: No ]

    Patients reported their pain relief using a 5-point categorical scale of 0 to 4 (0 = No Relief, 1 = A Little Relief, 2 = Some Relief, 3 = A Lot of Relief and 4 = Complete Relief). TOTPAR 0-2 was represents the cumulative time-weighted sum of the pain relief (PR) scores between each assessment timepoint following the postoperative administration of study drug (i.e. 15 to 30 min, 30 to 45 min, etc.) over the first 2 hours. Pain relief assessments were measured at 15, 30, 45, 60, 90, 120 minutes after the start of the infusion of study drug following surgery.

    Positive TOTPAR values represent an increase in pain relief.


  • Global Evaluation Responder Analysis [ Time Frame: At 24 hours ] [ Designated as safety issue: No ]
    Responders = Excellent or Very Good; Non-Responders = Fair or Poor. Patient who reported a score of "Good" were not included in the analysis as the midpoint cannot be unambiguously assigned for a binary outcome measurement.

  • Total Number of Patients Reporting At Least One Episode of Nausea [ Time Frame: Up to 24 hours ] [ Designated as safety issue: No ]
  • Total Number of Patients Reporting At Least One Episode of Vomiting [ Time Frame: Up to 24 hours ] [ Designated as safety issue: No ]

Enrollment: 203
Study Start Date: July 2011
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CR845
Peripheral kappa opioid receptor agonist
Drug: CR845
Single i.v. dose (0.04 mg/kg) administered preoperatively
Other Name: Preoperative Active Dose
Drug: CR845
Single i.v. dose (0.04 mg/kg) administered postoperatively for pain
Other Name: Postoperative Active for Pain
Placebo Comparator: Placebo
Matched Placebo
Drug: Placebo
Single i.v. dose administered preoperatively
Other Name: Preoperative Placebo Dose
Drug: Placebo
Single i.v. dose administered postoperatively for pain
Other Name: Postoperative Placebo for Pain

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 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able to provide written informed consent prior to any study procedures;
  • Able to communicate clearly with the Investigator and staff;
  • Female between 21 and 65 years of age, inclusive;
  • Scheduled for elective laparoscopic hysterectomy under general anesthesia;
  • Negative result on serum pregnancy test at screening and negative urine pregnancy test at Baseline (for women of child-bearing potential only) and not currently breast feeding, or planning to do so within 30 days of dosing;
  • Negative urine drug screen for drugs of abuse at Screening and at Baseline;
  • American Society of Anesthesiologists (ASA) risk class of I to III;
  • Body mass index (BMI) between 17 and 40 inclusive.

Exclusion Criteria:

  • Has known allergies to opioids, or hypersensitivity to other materials (such as infusion line) or medications to be used in the study;
  • Has a known or suspected history of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-diagnosed alcohol, opiate or other drug abuse or dependence within 12 months prior to screening;
  • Is unable to refrain from alcohol consumption for a period beginning 24 hours prior to surgery through the end of the Treatment Period;
  • Is scheduled to undergo a hysterectomy that will utilize any type of robotic technology and/or a concomitant surgical procedure that would produce a significantly greater degree of surgical trauma than the laparoscopic hysterectomy or laparoscopic assisted vaginal hysterectomy alone;
  • Has taken non-opioid analgesics (including cyclooxygenase-2 [COX-2] inhibitors) or nonsteroidal anti-inflammatory drugs (NSAIDs) within 12 hours of the Baseline assessments;
  • Has taken any opioid analgesics or used systemic steroids within 4 days of surgery OR has previously used opiates chronically for a period of ≥3 months;
  • Has used antipsychotics, antiepileptics, sedatives, hypnotics, or antianxiety agents, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants for < 30 days prior to surgery or had a dose change within the previous 30 days;
  • Has taken any prescription or over-the-counter medication within 3 days prior to surgery that, in the opinion of the Investigator, is expected to confound the analgesic response;
  • Has taken herbal agents or nutraceuticals (i.e., chaparral, comfrey, germander, gin bu huan, kava, pennyroyal, skullcap, St. John's wort, or valerian) 7 days prior to surgery;
  • In the opinion of Investigator shows clinical signs of hypovolemia;
  • Has an oxygen saturation < 92% on room air at Screening or prior to receiving the first infusion of study drug;
  • Has any history of clinically significant cardiovascular disease,
  • Has a clinically significant abnormal electrocardiogram (ECG) or a history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
  • Has a history of any serious medical conditions that in the opinion of the Investigator would preclude study participation;
  • Has serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, or gamma glutamyl transferase (GGT) >2.5 x the upper limit of normal (ULN) at screening;
  • Has bilirubin, blood urea nitrogen (BUN), or creatinine >1.5 x the reference ULN at Screening;
  • Has abnormally low hemoglobin < 10 mg/dl at Screening;
  • Has serum sodium levels > 146 mmol/L at Screening;
  • Has impaired renal function (creatinine clearance [CrCl] < 50 ml/min) at Screening;
  • Has a positive test for human immunodeficiency virus (HIV) or known history of HIV infection;
  • Has received another investigational drug within 30 days of scheduled surgery;
  • Has a significant chronic pain condition in areas unrelated to the operative site at the time of Screening that in the Investigator's opinion could confound the interpretation of study results
  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: NCT01361568

Locations
United States, Alabama
Shoals Clinical Research Associates
Florence, Alabama, United States, 35630
Wilmax
Mobile, Alabama, United States, 36608
Horizon Research Group
Mobile, Alabama, United States, 36606
Drug Research and Analysis Corp
Montgomery, Alabama, United States, 36106
Shoals Medical Trials, INC
Sheffield, Alabama, United States, 35660
United States, Arizona
Precision Clinical Trials
Phoenix, Arizona, United States, 85032
United States, California
Woodland Healthcare California Clinical Research, Inc
Davis, California, United States, 95616
Olive View-UCLA Medical Center
Sylmar, California, United States, 91342
United States, Florida
Visions Clinical Research
Boynton Beach, Florida, United States, 33472
Riverside Clinical Research
Edgewater, Florida, United States, 32132
University of Miami, Dept of
Miami, Florida, United States, 33136
United States, Kansas
Cypress Medical Research
Wichita, Kansas, United States, 67226
United States, New Jersey
Cooper University Hospital
Camden, New Jersey, United States, 08103
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
Ohio State University Medical, Dept of Anesthesia
Columbus, Ohio, United States, 43210
United States, South Carolina
Palmetto Clinical Research,
Greenville, South Carolina, United States, 29615
United States, Tennessee
Chattanooga Medical Research
Chattanooga, Tennessee, United States, 37404
United States, Texas
Texas Health Care, PLLC
Fort Worth, Texas, United States, 76104
Sponsors and Collaborators
Cara Therapeutics, Inc.
Investigators
Principal Investigator: Tong-Joo Gan, MD, MHS Duke University
  More Information

No publications provided

Responsible Party: Cara Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01361568     History of Changes
Other Study ID Numbers: CR845 CLIN2002
Study First Received: May 25, 2011
Results First Received: February 18, 2013
Last Updated: May 20, 2014
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:
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Analgesics
Peripheral Nervous System Agents
Physiological Effects of Drugs
Sensory System Agents
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014