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

NCT05324358 | Suspended Phase 3 DMC FDA Drug

• 1 other identifier: NTM-001-CT001
• Study Type: interventional
• Target: 341
• Locations: 1 country
• Sites: 10

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.

Conditions

Pain, Postoperative

Outcome Measures

Primary Outcomes (1)

• 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.

  0 to 24 hours after start of administration

Study Arms (3)

NTM-001 Treatment Arm

EXPERIMENTAL

* 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).

Drug: Ketorolac Tromethamine; Other: IV Placebo for Morphine

Morphine Treatment Arm

ACTIVE COMPARATOR

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

Drug: Morphine Sulfate; Other: Intravenous Placebo for NTM-001

Placebo Treatment Arm

PLACEBO COMPARATOR

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.

Other: Intravenous Placebo for NTM-001; Other: IV Placebo for Morphine

Interventions

Intravenous Placebo for NTM-001 OTHER

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).

Morphine Treatment Arm; Placebo Treatment Arm

Ketorolac Tromethamine DRUG

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).

Also known as: NTM-001 (Ketorolac Tromethamine IV Continuous Infusion)

NTM-001 Treatment Arm

Morphine Sulfate DRUG

Morphine single use vials at 4 mg/mL, filled with 1 mL.

Also known as: Morphine Sulfate Injection USP

Morphine Treatment Arm

IV Placebo for Morphine OTHER

Placebo single use vials with saline (matching active morphine).

NTM-001 Treatment Arm; Placebo Treatment Arm

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Neumentum, Inc.: lead
• NEMA Research, Inc.: collaborator

Study Sites (10)

Sun City Clinical Research

Sun City, Arizona, 85351, United States

Location

Trovare Clinical Research

Bakersfield, California, 93301, United States

Location

Alliance Research Intitute

Canoga Park, California, 91304, United States

Location

Pasadena Clinical Trials

Pomona, California, 91767, United States

Location

Dr. Vince Clinical Research

Overland Park, Kansas, 66212, United States

Location

Chesapeake Research

Pasadena, Maryland, 21122, United States

Location

Curalta Clinical Trials

Westwood, New Jersey, 07675, United States

Location

Midwest Clinical Research Center

Dayton, Ohio, 45417, United States

Location

The Orthopedic Center

Tulsa, Oklahoma, 74104, United States

Location

Endeavor Clinical Trials

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Ketorolac Tromethamine; Morphine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2022
• First Posted: April 12, 2022
• Study Start: December 14, 2022
• Primary Completion: September 6, 2024
• Study Completion (Estimated): May 1, 2027
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)