Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01361568
Recruitment Status : Completed
First Posted : May 27, 2011
Results First Posted : May 19, 2014
Last Update Posted : May 29, 2014
Sponsor:
Information provided by (Responsible Party):
Cara Therapeutics, Inc.

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

Condition or disease Intervention/treatment Phase
Postoperative Pain Drug: CR845 Drug: Placebo Phase 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 203 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : July 2011
Actual Primary Completion Date : April 2012
Actual Study Completion Date : April 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hysterectomy

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Total Morphine Consumption in the First 24 Hours Following Postoperative Study Drug Treatment [ Time Frame: 24 hours ]

Secondary Outcome Measures :
  1. 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 ]

    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).


  2. 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) ]
  3. Total Pain Relief Within the First 2 Hours (TOTPAR 0-2) Following Postoperative Study Drug Treatment Using LOCF [ Time Frame: 0 to 2 hours ]

    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.


  4. Global Evaluation Responder Analysis [ Time Frame: At 24 hours ]
    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.

  5. Total Number of Patients Reporting At Least One Episode of Nausea [ Time Frame: Up to 24 hours ]
  6. Total Number of Patients Reporting At Least One Episode of Vomiting [ Time Frame: Up to 24 hours ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01361568


Locations
Show Show 18 study locations
Sponsors and Collaborators
Cara Therapeutics, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Tong-Joo Gan, MD, MHS Duke University

Layout table for additonal information
Responsible Party: Cara Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01361568    
Other Study ID Numbers: CR845 CLIN2002
First Posted: May 27, 2011    Key Record Dates
Results First Posted: May 19, 2014
Last Update Posted: May 29, 2014
Last Verified: May 2014
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:
Layout table for MeSH terms
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Neurologic Manifestations
Signs and Symptoms
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs