A Study Evaluating the Overall Pain Relief and Safety of Intravenous (IV) CR845 in Patients Undergoing Abdominal Surgery

NCT02542384 | Completed Phase 2 DMC

• 1 other identifier: CR845-CLIN3001
• Study Type: interventional
• Target: 451
• Locations: 1 country
• Sites: 23

Brief Summary

The study schedule is comprised of a 14-day Screening Period, a treatment period and an observation period. All eligible subjects will be randomized into one of 3 treatment groups (1 of 2 dose levels or matched placebo). Study drug CR845 will be administered intravenously prior to surgery, and at specific time intervals post surgery. Additional rescue pain and anti-nausea medication will be made available. Post surgical changes in pain intensity, nausea and vomiting will be assessed.

Conditions

Post Abdominal Surgery Pain

Keywords

abdominal surgery; laparoscopy; Hysterectomy; Prostatectomy; Hemi-colectomy; Ventral Hernia repair; CR845; analgesic; kappa opioid; partial bowel resection; difelikefalin

Outcome Measures

Primary Outcomes (1)

• A comparison of the change in Pain Intensity over time using the Numeric Rating Scale

  Using the Numeric Rating Scale (NRS) to quantify the difference between CR845-treated patients and placebo-treated patients.

  24 hours

Secondary Outcomes (3)

• A study of the comparison of Post Surgical Nausea and Vomiting (PONV) scores

  6 hours

• A comparison of the number of rescue medication doses administered

  24 hours

• Patient Global Assessment of study drug

  24 hours (or early termination)

Other Outcomes (1)

• Ongoing safety evaluation of CR845 assessed by physical examination, adverse events, vital signs, and laboratory evaluations

  10 Days

Study Arms (3)

CR845 IV 1 mcg/kg

ACTIVE COMPARATOR

CR845 IV solution will be supplied in 2 mL glass vials.Study drug will be administered as an IV bolus into an infusion line, the volume is dependent upon the patient's body weight.

Drug: CR845 IV 1 mcg/kg

CR845 IV 0.5 mcg/kg

ACTIVE COMPARATOR

CR845 solution will be supplied in 2 mL glass vials. Study drug will be administered as an IV bolus into an infusion line, the volume is dependent upon the patient's body weight.

Drug: CR845 IV 0.5 mcg/kg

Placebo IV

PLACEBO COMPARATOR

Placebo will be supplied in matched vials containing the same volume of buffer but with no active drug. It will be administered as an IV bolus into an infusion line, the volume is dependent upon the patient's body weight.

Drug: Placebo IV

Interventions

CR845 IV 1 mcg/kg DRUG

CR845 IV 1 mcg/kg will be administered as an IV bolus 2x loading dose one hour prior to anesthetic induction for surgery, then a dose within 30 minutes of the patient being considered stable in the post operative recovery room. Subsequent dosing will be administered at 6, 12 and 18 hours. Antinausea rescue medication (ondansetron 4 mg IV) may be requested, as well as analgesic rescue medication (morphine 5mg IV), post surgery, as needed. Saline infusion (IV 0.45%) for fluid replenishment will be provided.

CR845 IV 1 mcg/kg

CR845 IV 0.5 mcg/kg DRUG

CR845 IV 0.5 mcg/kg will be administered as an IV bolus 2x loading dose one hour prior to anesthetic induction for surgery, then a dose within 30 minutes of the patient being considered stable in the post operative recovery room. Subsequent dosing will be administered at 6, 12 and 18 hours. Antinausea rescue medication (ondansetron 4 mg IV) may be requested, as well as analgesic rescue medication (morphine 5mg IV), post surgery, as needed. Saline infusion (IV 0.45%) for fluid replenishment will be provided.

CR845 IV 0.5 mcg/kg

Placebo IV DRUG

Placebo IV will be administered as an IV bolus 2x loading dose one hour prior to anesthetic induction for surgery, then a dose within 30 minutes of the patient being considered stable in the post operative recovery room. Subsequent dosing will be administered at 6, 12 and 18 hours. Antinausea rescue medication (ondansetron 4 mg IV) may be requested, as well as analgesic rescue medication (morphine 5mg IV), post surgery, as needed. Saline infusion (IV 0.45%) for fluid replenishment will be provided.

Placebo IV

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- A patient will be eligible for study participation if the subject meets the following criteria:
• Voluntarily provide written informed consent to participate in the study prior to any study procedures.
• Able to speak, read, and communicate clearly in English or Spanish; able to read and understand the study procedures.
• Male or female between 21 and older at the time of Screening.
• Scheduled for abdominal surgery (hysterectomy; prostatectomy; hemi-colectomy (including partial bowel resections) or ventral hernia repair) with no collateral procedures.
• Patient is categorized as American Society of Anesthesiologists (ASA) risk class of I, II or III.
• Has a body mass index (BMI) within 18.0-40.0 kg/m2 and weight between 50 kg and 112 kg, inclusive.
• For women of childbearing potential- has a negative result on serum pregnancy testing at Screening and urine pregnancy test at Admission and does not currently breast feed, or is planning to do so within 30 days of receiving the last dose of study drug.
• If female, the patient must be:
• Of childbearing potential and practicing an acceptable form of birth control (defined as the use of an intrauterine device; a barrier method with spermicide; condoms, any form of hormonal contraceptives; or abstinence from sexual intercourse) for 3 days following the last dose of study drug.
• Of non-childbearing potential defined as surgically or biologically sterile (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or postmenopausal for at least 1 year).
• Is free of other physical, mental, or medical conditions, which, in the opinion of the Investigator, would make study participation inadvisable.
• Following surgery, the patient will be eligible for the second dose of study drug.

You may not qualify if:

• A patient will be excluded from the study if any of the following criteria are met:
• Has a serum sodium level \> 143 mmol/L at Screening.
• Has a serum sodium level \< 136 mmol/L at Screening.
• Patient is unwilling or unable to comply with the study procedures and assessments until the end of the 48-hour treatment and observation period.
• Has moderate to severe obstructive sleep apnea, which, in the opinion of the Investigator is not being adequately treated (i.e., Nasal/Facial C-PAP), and will pose an unacceptable risk.
• Has known allergies or hypersensitivity to drugs that may be used during the study, including those used during the surgical procedure and in the post-operative period \[e.g., inhaled anesthetics (such as sevoflurane), midazolam, opioids (such as fentanyl and morphine sulfate), propofol or other sedatives, local anesthetics, antiemetics (such as ondansetron) non- steroidal anti-inflammatory drugs (such as ketorolac) or acetaminophen\].
• Uses antipsychotics, antiepileptics, sedatives, hypnotics, or antianxiety agents, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants with a dose change \< 30 days prior to surgery.
• Has a history or current diagnosis of substance dependence (except caffeine or nicotine) or alcohol abuse, according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
• Has a positive urine drug screen for drugs of abuse at Screening.
• Is unwilling to abstain from alcohol consumption for a period beginning 24 hours prior to Admission until the time of Discharge from the hospital.
• Suffers from chronic dizziness, vestibular disorders, or has experienced severe continuous diarrhea, retching, vomiting, or moderate or severe nausea and/or dizziness for any reason within 72 hours prior to Admission.
• Has been diagnosed with a condition of hyperhidrosis (excessive sweating) or primary hypodipsia (abnormally diminished thirst).
• Has donated or had significant loss of whole blood (240 mL or more) within 30 days or plasma within 14 days prior to Admission.
• Has a history (within 6 months) of clinically meaningful orthostatic changes in vital signs - OR - a decrease in systolic blood pressure by \> 20 mm Hg or a decrease in diastolic blood pressure by 10 mm Hg together with an increase in heart rate of \> 30 beats per minute when transitioning from supine to standing measurements at the time of Screening.
• Hasmedicalconditions(e.g.,cardiovascular,pulmonary,hepatic,renal, hematologic, gastrointestinal, endocrine (adrenal hyperplasia), immunologic, dermatologic, neurologic, oncologic or psychiatric condition) or a significant laboratory abnormality that, in the Investigator's opinion, would jeopardize the safety of the patient or is likely to confound the study measurements.

Sponsors & Collaborators

• Cara Therapeutics, Inc.: lead

Study Sites (23)

Cara Therapeutics Study Site

Sheffield, Alabama, United States

Location

Cara Therapeutics Study Site

New Haven, Connecticut, United States

Location

Cara Therapeutics Study Site

Bradenton, Florida, 34209, United States

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Cara Therapeutics Study Site

Gainesville, Florida, United States

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Cara Therapeutics Study Site

Maitland, Florida, United States

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Cara Therapeutics Study Site

Miami Gardens, Florida, United States

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Cara Therapeutics Study Site

Pensacola, Florida, 32503, United States

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Cara Therapeutics Study Site

St. Petersburg, Florida, 33713, United States

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Cara Therapeutics Study Site

Chicago, Illinois, United States

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Cara Therapeutics Study Site

Boston, Massachusetts, United States

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Cara Therapeutics Study Site

Camden, New Jersey, 08103, United States

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Cara Therapeutics Study Site

Neptune City, New Jersey, United States

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Cara Therapeutics Study Site

Durham, North Carolina, 27710, United States

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Cara Therapeutics Study Site

Cleveland, Ohio, United States

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Cara Therapeutics Study Site

Columbus, Ohio, United States

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Cara Therapeutics Study Site

Pittsburgh, Pennsylvania, United States

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Cara Therapeutics Study Site

Chattanooga, Tennessee, United States

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Cara Therapeutics Study Site

Bellaire, Texas, United States

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Cara Therapeutics Study Site

Fort Worth, Texas, United States

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Cara Therapeutics Study Site

Houston, Texas, United States

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Cara Therapeutics Study Site

Plano, Texas, United States

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Cara Therapeutics Study Site

San Antonio, Texas, United States

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Cara Therapeutics Study Site

Salt Lake City, Utah, 84124, United States

Location

Study Officials

• Joseph Stauffer, DO, MBA

  Cara Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2015
• First Posted: September 7, 2015
• Study Start: September 1, 2015
• Primary Completion: April 1, 2018
• Study Completion: June 1, 2018
• Last Updated: May 31, 2019

Record last verified: 2019-05

Locations

US (23)