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
Overview
- Phase
- Phase 3
- Intervention
- IV Placebo for Morphine
- Conditions
- Pain, Postoperative
- Sponsor
- Neumentum, Inc.
- Enrollment
- 341
- Locations
- 20
- Primary Endpoint
- Summed Pain Intensity Difference (SPID24)
- Status
- Suspended
- Last Updated
- 9 days ago
Overview
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.
Investigators
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.
Arms & Interventions
NTM-001 Treatment Arm
* 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).
Intervention: IV Placebo for Morphine
Placebo Treatment Arm
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: Intravenous Placebo for NTM-001
Morphine Treatment Arm
* A single IV morphine bolus (4 mg) every 4h for up to 24h. * Subjects will also receive placebo to NTM-001.
Intervention: Intravenous Placebo for NTM-001
Placebo Treatment Arm
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: IV Placebo for Morphine
NTM-001 Treatment Arm
* 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).
Intervention: Ketorolac Tromethamine
Morphine Treatment Arm
* A single IV morphine bolus (4 mg) every 4h for up to 24h. * Subjects will also receive placebo to NTM-001.
Intervention: Morphine Sulfate
Outcomes
Primary Outcomes
Summed Pain Intensity Difference (SPID24)
Time Frame: 0 to 24 hours after start of administration
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.