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Ketorolac Applied by Continuous IV Infusion for Treatment of Moderately Severe Postoperative Pain Following Bunionectomy

Primary Purpose

Pain, Postoperative

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Ketorolac Tromethamine
Morphine Sulfate
Intravenous Placebo for NTM-001
IV Placebo for Morphine
Sponsored by
NEMA Research, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pain, Postoperative

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Written informed consent obtained prior to any study-related procedure being performed.
  2. Male or female subjects between 18 and <65 years of age at time of consent.
  3. Body weight ≥50 kg.
  4. Physical status rated as ≤2 on the American Society of Anesthesiologists (ASA) rating scale (Owens, Felts et al. 1978).
  5. Scheduled to undergo primary unilateral first metatarsal bunionectomy.
  6. Women must be postmenopausal, surgically sterile, abstinent, or practicing or agree to practice an effective method of birth control if they are sexually active before entry, throughout the study, and for 7 days after the last dose of study drug (effective methods of birth control include prescription hormonal contraceptives, intrauterine devices, double-barrier method, and male partner sterilization). Women of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at screening and a negative urine pregnancy test before surgery.
  7. Subject is willing and able to complete all study procedures including training on pain scales, follow instructions, communicate meaningfully with study personnel, and return for all visits as listed in the protocol.

Exclusion Criteria:

  1. History of peptic ulcer disease, GI bleeding, perforation, or active peptic ulcer disease.
  2. History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
  3. History of, or suspected or confirmed, cerebrovascular bleeding, hemorrhagic diathesis, or incomplete hemostasis.
  4. Increased risk of bleeding at the discretion of the Investigator based on prior/concomitant disease, laboratory values, medication or surgical complications.
  5. Clinical laboratory values reflecting at least mild renal insufficiency as indicated by a creatinine clearance ≤89 mL/min.
  6. Risk for renal failure due to volume depletion at the discretion of the Investigator.
  7. Concomitant use of aspirin or NSAIDs.
  8. History of seizure disorder or epilepsy, as suggested by the presence of any of the following:

    • Mild or moderate traumatic brain injury, stroke, transient ischemic attach, or brain neoplasm within 1 year of screening.
    • Severe traumatic brain injury, episode(s) of unconsciousness of more than 24 hours duration, or posttraumatic amnesia of more than 24 hours duration within 15 years of screening.
  9. History of alcohol or drug abuse in the Investigator's judgement based on subject history and physical examination.
  10. Significant chronic obstructive pulmonary disease or cor pulmonale, a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression.
  11. At least moderately impaired hepatic function (Child-Pugh >6), or subjects with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values greater than 3 times the upper limit of normal (ULN).
  12. Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days.
  13. The subject is not on a stable dose (at least 2 weeks prior to Screening Visit) of medications that may lower the seizure threshold (e.g., anti-psychotic agents) or which impact the serotonergic system (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants).
  14. Evidence of significant anemia (indicated by hemoglobin concentration ≤8 g/dL).
  15. Evidence of active infections that may spread to other areas of the body (e.g., osteomyelitis, pyogenic infection of the hip, Hepatitis B or C, or other overt infections) or a history of human immunodeficiency virus (HIV) 1 or 2.
  16. History of malignancy within 2 years prior to the start of the study, with the exception of basal cell and cutaneous squamous cell carcinoma.
  17. History of systemic lupus erythematosus, antiphospholipid syndrome, vasculitis, vasculopathy, or deep vein thrombosis.
  18. Uncontrolled or poorly controlled post-traumatic stress disorder, generalized anxiety disorder, depression, psychiatric, or other significant medical conditions.
  19. Chronic systemic steroid therapy, excluding inhalers or a 1-time intraoperative dose, within 4 weeks before screening.
  20. History of pending litigation due to pain or disability.
  21. Clinically significant disease that, in the Investigator's opinion, may affect efficacy or safety assessments.
  22. Employees of the Investigator or study site with direct involvement in the proposed study or other studies under the direction of that Investigator or study site, including family members of the employees or the Investigator.
  23. Received an experimental drug or used an experimental medical device within 30 days before screening or have participated in a previous study of ketorolac.
  24. Contraindications to, or history of allergy or hypersensitivity to ketorolac and/or morphine and their excipients.
  25. A positive COVID-19 test (rapid antigen test) or COVID-19 related symptoms at screening and/or at check in of Visit 2 (Surgical Period).
  26. Subjects who are planning on receiving a COVID-19 vaccine during the study duration.

Sites / Locations

  • Chesapeake ResearchRecruiting
  • NextStage Clinical Research- The Orthopedic Center
  • First Surgical (ERG)
  • HD Research
  • Endeavor Clinical Trials (ERG)
  • NextStage Clinical Research- South Texas Spine and Surgical HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

NTM-001 Treatment Arm

Morphine Treatment Arm

Placebo Treatment Arm

Arm Description

NTM-001 loading dose of 12.5 mg administered over approximately 60 seconds, followed by a continuous IV infusion at a rate of 3.5 mg/h for 24h, by a pre-programmed infusion pump. Subjects will also receive placebo to IV Morphine (injections).

A single IV morphine bolus (4 mg) every 4h for up to 24h. Subjects will also receive placebo to NTM-001.

Subjects randomized will receive placebos of both active treatments concomitantly. Placebo to NTM-001: Placebo "loading dose" applied over approximately 60 seconds, followed by a continuous IV infusion at a rate of 3.5 mL/h for 24h by a pre-programmed infusion pump. Placebo to IV morphine injections: A single IV placebo bolus every 4h for up to 24h.

Outcomes

Primary Outcome Measures

Summed Pain Intensity Difference (SPID24)
The primary endpoint is the Summed Pain Intensity Difference over 24h (SPID24) from start to end of administration of investigational medicinal product (IMP). Calculated as the weighted sum of the PID (difference between baseline at qualifying period and current pain intensity) collected at protocol scheduled time points through up to 24h after starting infusion of the IMP, using the following formula: SPID24 = Σ Wi * PIDi (1) where the Σ sums over all observations collected from the first assessment after the first IMP administration to Hour 24 and Wi is the time elapsed from the previous observation PIDi-1 to the current observation PIDi.

Secondary Outcome Measures

Full Information

First Posted
April 4, 2022
Last Updated
December 28, 2022
Sponsor
NEMA Research, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05324358
Brief Title
Ketorolac Applied by Continuous IV Infusion for Treatment of Moderately Severe Postoperative Pain Following Bunionectomy
Official Title
A Randomized, Double-Blind, Double-Dummy, Parallel-Group, Active and Placebo-Controlled Trial to Evaluate the Analgesic Efficacy and Safety of NTM-001 for the Treatment of Moderately Severe Postoperative Pain Following Bunionectomy
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 15, 2022 (Actual)
Primary Completion Date
June 1, 2023 (Anticipated)
Study Completion Date
September 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NEMA Research, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This clinical study is a randomized, double-blind, double-dummy, parallel group, multi-center, active and placebo-controlled trial evaluating the analgesic efficacy and safety of NTM-001 in subjects with moderately severe postoperative pain after bunionectomy surgery. This study is designed to compare the efficacy of NTM-001 to placebo. Intravenous (IV) morphine serves as an active comparator to determine assay sensitivity and support assessment of opioid-level analgesia for NTM-001. Effectiveness, safety, and tolerability parameters will be descriptively compared between treatment arms.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
360 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
NTM-001 Treatment Arm
Arm Type
Experimental
Arm Description
NTM-001 loading dose of 12.5 mg administered over approximately 60 seconds, followed by a continuous IV infusion at a rate of 3.5 mg/h for 24h, by a pre-programmed infusion pump. Subjects will also receive placebo to IV Morphine (injections).
Arm Title
Morphine Treatment Arm
Arm Type
Active Comparator
Arm Description
A single IV morphine bolus (4 mg) every 4h for up to 24h. Subjects will also receive placebo to NTM-001.
Arm Title
Placebo Treatment Arm
Arm Type
Placebo Comparator
Arm Description
Subjects randomized will receive placebos of both active treatments concomitantly. Placebo to NTM-001: Placebo "loading dose" applied over approximately 60 seconds, followed by a continuous IV infusion at a rate of 3.5 mL/h for 24h by a pre-programmed infusion pump. Placebo to IV morphine injections: A single IV placebo bolus every 4h for up to 24h.
Intervention Type
Drug
Intervention Name(s)
Ketorolac Tromethamine
Other Intervention Name(s)
NTM-001 (Ketorolac Tromethamine IV Continuous Infusion)
Intervention Description
Ketorolac tromethamine, alcohol free formulation, 1.0 mg/mL in saline solution (~0.9% NaCl) adjusted to a pH of ~7.4. Contained in a sterile, 200 mL polyolefin bag (filled with 125 mL of NTM-001).
Intervention Type
Drug
Intervention Name(s)
Morphine Sulfate
Other Intervention Name(s)
Morphine Sulfate Injection USP
Intervention Description
Morphine single use vials at 4 mg/mL, filled with 1 mL.
Intervention Type
Other
Intervention Name(s)
Intravenous Placebo for NTM-001
Intervention Description
Placebo alcohol free saline solution (~0.9% NaCl; matching active NTM-001). Contained in a sterile, 200 mL polyolefin bag (filled with 125 mL Placebo solution).
Intervention Type
Other
Intervention Name(s)
IV Placebo for Morphine
Intervention Description
Placebo single use vials with saline (matching active morphine).
Primary Outcome Measure Information:
Title
Summed Pain Intensity Difference (SPID24)
Description
The primary endpoint is the Summed Pain Intensity Difference over 24h (SPID24) from start to end of administration of investigational medicinal product (IMP). Calculated as the weighted sum of the PID (difference between baseline at qualifying period and current pain intensity) collected at protocol scheduled time points through up to 24h after starting infusion of the IMP, using the following formula: SPID24 = Σ Wi * PIDi (1) where the Σ sums over all observations collected from the first assessment after the first IMP administration to Hour 24 and Wi is the time elapsed from the previous observation PIDi-1 to the current observation PIDi.
Time Frame
0 to 24 hours after start of administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent obtained prior to any study-related procedure being performed. Male or female subjects between 18 and <65 years of age at time of consent. Body weight ≥50 kg. Physical status rated as ≤2 on the American Society of Anesthesiologists (ASA) rating scale (Owens, Felts et al. 1978). Scheduled to undergo primary unilateral first metatarsal bunionectomy. Women must be postmenopausal, surgically sterile, abstinent, or practicing or agree to practice an effective method of birth control if they are sexually active before entry, throughout the study, and for 7 days after the last dose of study drug (effective methods of birth control include prescription hormonal contraceptives, intrauterine devices, double-barrier method, and male partner sterilization). Women of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at screening and a negative urine pregnancy test before surgery. Subject is willing and able to complete all study procedures including training on pain scales, follow instructions, communicate meaningfully with study personnel, and return for all visits as listed in the protocol. Exclusion Criteria: History of peptic ulcer disease, GI bleeding, perforation, or active peptic ulcer disease. History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. History of, or suspected or confirmed, cerebrovascular bleeding, hemorrhagic diathesis, or incomplete hemostasis. Increased risk of bleeding at the discretion of the Investigator based on prior/concomitant disease, laboratory values, medication or surgical complications. Clinical laboratory values reflecting at least mild renal insufficiency as indicated by a creatinine clearance ≤89 mL/min. Risk for renal failure due to volume depletion at the discretion of the Investigator. Concomitant use of aspirin or NSAIDs. History of seizure disorder or epilepsy, as suggested by the presence of any of the following: Mild or moderate traumatic brain injury, stroke, transient ischemic attach, or brain neoplasm within 1 year of screening. Severe traumatic brain injury, episode(s) of unconsciousness of more than 24 hours duration, or posttraumatic amnesia of more than 24 hours duration within 15 years of screening. History of alcohol or drug abuse in the Investigator's judgement based on subject history and physical examination. Significant chronic obstructive pulmonary disease or cor pulmonale, a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. At least moderately impaired hepatic function (Child-Pugh >6), or subjects with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values greater than 3 times the upper limit of normal (ULN). Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days. The subject is not on a stable dose (at least 2 weeks prior to Screening Visit) of medications that may lower the seizure threshold (e.g., anti-psychotic agents) or which impact the serotonergic system (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants). Evidence of significant anemia (indicated by hemoglobin concentration ≤8 g/dL). Evidence of active infections that may spread to other areas of the body (e.g., osteomyelitis, pyogenic infection of the hip, Hepatitis B or C, or other overt infections) or a history of human immunodeficiency virus (HIV) 1 or 2. History of malignancy within 2 years prior to the start of the study, with the exception of basal cell and cutaneous squamous cell carcinoma. History of systemic lupus erythematosus, antiphospholipid syndrome, vasculitis, vasculopathy, or deep vein thrombosis. Uncontrolled or poorly controlled post-traumatic stress disorder, generalized anxiety disorder, depression, psychiatric, or other significant medical conditions. Chronic systemic steroid therapy, excluding inhalers or a 1-time intraoperative dose, within 4 weeks before screening. History of pending litigation due to pain or disability. Clinically significant disease that, in the Investigator's opinion, may affect efficacy or safety assessments. Employees of the Investigator or study site with direct involvement in the proposed study or other studies under the direction of that Investigator or study site, including family members of the employees or the Investigator. Received an experimental drug or used an experimental medical device within 30 days before screening or have participated in a previous study of ketorolac. Contraindications to, or history of allergy or hypersensitivity to ketorolac and/or morphine and their excipients. A positive COVID-19 test (rapid antigen test) or COVID-19 related symptoms at screening and/or at check in of Visit 2 (Surgical Period). Subjects who are planning on receiving a COVID-19 vaccine during the study duration.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Roshna Noor
Phone
239-597-3564
Email
rnoor@nemaresearch.net
Facility Information:
Facility Name
Chesapeake Research
City
Pasadena
State/Province
Maryland
ZIP/Postal Code
21122
Country
United States
Individual Site Status
Recruiting
Facility Name
NextStage Clinical Research- The Orthopedic Center
City
Jenks
State/Province
Oklahoma
ZIP/Postal Code
74037
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
First Surgical (ERG)
City
Bellaire
State/Province
Texas
ZIP/Postal Code
77401
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
HD Research
City
Houston
State/Province
Texas
ZIP/Postal Code
77008
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dominick D'Aunno
First Name & Middle Initial & Last Name & Degree
Dominick D'Aunno
Facility Name
Endeavor Clinical Trials (ERG)
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
NextStage Clinical Research- South Texas Spine and Surgical Hospital
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78258
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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Ketorolac Applied by Continuous IV Infusion for Treatment of Moderately Severe Postoperative Pain Following Bunionectomy

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