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Trial · Interventional

CompletedPhase 2Results postedRegistry data

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

Overview

Status
Completed
Phase
Phase 2
Enrollment
203 participants (actual)
Sponsor
Cara Therapeutics, Inc. · Industry
Design
Randomized · Quadruple masking
Countries
1 country

United States

Start
Jul 2011
Primary completion
Apr 2012
Completion
Apr 2012
First posted
27 May 2011 (estimated)
Last update posted
29 May 2014 (estimated)
Conditions
Postoperative Pain

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201120122013
  1. Ph 2

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

    NCT01361568

    Jul 2011 to Apr 2012

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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

Interventions

  • CR845Drug
  • PlaceboDrug
  • CR845Drug
  • PlaceboDrug

Arms2

  • Experimental

    CR845

    Peripheral kappa opioid receptor agonist

  • Placebo comparator

    Placebo

    Matched Placebo

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Total Morphine Consumption in the First 24 Hours Following Postoperative Study Drug Treatment

    Time frame · 24 hours

Secondary outcomes(6)
  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

    Registry description

    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

    Registry description

    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

    Registry description

    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

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· 24 hours

Total Morphine Consumption in the First 24 Hours Following Postoperative Study Drug Treatment

GroupValue (mg)Spread
Placebo-Placebo21.91.89
Placebo-CR84517.61.65
CR845-CR84513.92.20
CR845-Placebo19.83.03
Secondary and other outcome results(6)
Secondary outcomeMean· 0 to 24 hours

Summed Pain Intensity Difference From 0-24 Hours (SPID 0-24) Following Postoperative Study Drug Treatment Using Last Observation Carried Forward (LOCF)

GroupValue (units on a scale * hours)Spread
Placebo-Placebo-413.167.8
Placebo-CR845-643.258.11
CR845-CR845-833.1124.8
CR845-Placebo-673.5152.36
Secondary outcomeMean· 2 to 24 hours (post-PACU)

Morphine Consumption Following Postoperative Study Drug Treatment in the 2-24 Hour Period After Recovery in the Post-Anesthesia Care Unit (Post-PACU)

GroupValue (mg)Spread
Placebo-Placebo14.381.35
Placebo-CR84511.071.17
CR845-CR8457.992.03
CR845-Placebo11.332.11
Secondary outcomeMean· 0 to 2 hours

Total Pain Relief Within the First 2 Hours (TOTPAR 0-2) Following Postoperative Study Drug Treatment Using LOCF

GroupValue (units on a scale * hours)Spread
Placebo-Placebo1.40.16
Placebo-CR8452.10.19
CR845-CR8452.40.48
CR845-Placebo1.50.40
Secondary outcomeNumber· At 24 hours

Global Evaluation Responder Analysis

GroupValue (Responder Count)
Placebo27
CR84568
Secondary outcomeNumber· Up to 24 hours

Total Number of Patients Reporting At Least One Episode of Nausea

GroupValue (percentage of patients)
Placebo51.2
CR84526.1
Secondary outcomeNumber· Up to 24 hours

Total Number of Patients Reporting At Least One Episode of Vomiting

GroupValue (percentage of patients)
Placebo8.3
CR8451.7

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Placebo-PlaceboPlacebo administered both preoperatively and postoperatively–0 / 7159 / 71
Placebo-CR845Placebo administered preoperatively and CR845 administered postoperatively–6 / 7162 / 71
CR845-CR845CR845 administered both preoperatively and postoperatively–3 / 2019 / 20
CR845-PlaceboCR845 administered preoperatively and placebo administered postoperatively–0 / 2115 / 21
CR845-No Postoperative TreatmentCR845 administered preoperatively and no study drug administered postoperatively–3 / 77 / 7
Placebo-No Postoperative TreatmentPlacebo administered preoperatively and no study drug administered postoperatively–1 / 1310 / 13

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
Female
Age
from 21 Years up to 65 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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