Placebo-Controlled Evaluation of Intranasal Dexmedetomidine for Postoperative Analgesia Following Bunionectomy Surgery

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Evaluation of the Efficacy and Safety of Intranasal Dexmedetomidine for Postoperative Analgesia Following Bunionectomy

The primary objective of this study is to evaluate the analgesic efficacy, on Post-Operative Day (POD) 1, of DEX-IN compared with placebo, using the summed pain intensity difference over the first 48 hours (SPID48) in subjects with acute moderate to severe pain following unilateral bunionectomy.

Study Overview

• Status: Completed
• Conditions: Pain, Post-operative
• Intervention / Treatment: Drug: Intranasal Placebo; Drug: Intranasal Dexmedetomidine

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Bakersfield, California, United States
      • Trovare Clinical Research, Inc.
    • Pasadena, California, United States
      • Lotus Clinical Research, LLC
  • Texas
    • San Antonio, Texas, United States
      • Endeavor Clinical Trials, P.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Voluntarily provide written informed consent.
• Male or female between 18 and 70 years of age, inclusive.
• Be scheduled to undergo a primary unilateral first metatarsal bunionectomy repair
• Be American Society of Anesthesiology (ASA) physical class 1 or 2.

• Female subject are eligible only if all the following apply:

  • Not pregnant;
  • Not lactating;
  • Not planning to become pregnant during the study;
  • Be surgically sterile; or at least two year post menopausal; or have a monogamous partner who is surgically sterile; or is practicing double-barrier contraception; or practicing abstinence; or using an insertable, injectable, transdermal, or combination oral contraceptive.
• Male subjects must be surgically sterile or commit to the use of a reliable method of birth control
• Have a body mass index ≤35 kg/m2
• Be able to understand the study procedures, comply with all study procedures, and agree to participate in the study program.

Exclusion Criteria:

• Have a known allergy to dexmedetomidine or any excipient in DEX-IN/placebo or to any peri- or postoperative medications used in this study.
• Have a clinically significant abnormal clinical laboratory test value.
• Have history of or positive test results for HIV, or hepatitis B or C.
• Have a history or clinical manifestations of significant renal, hepatic, cardiovascular, metabolic, neurologic, psychiatric, or other condition that would preclude participation in the study.
• Have a history of migraine or frequent headaches, seizures, or are currently taking anticonvulsants.
• Have another painful physical condition that may confound the assessments of post operative pain.
• Have a history of syncope or other syncopal attacks.
• Have evidence of a clinically significant 12 lead ECG abnormality.
• Have a history of alcohol abuse (regularly drinks > 4 units of alcohol per day; 8 oz. beer, 3 oz. wine, 1 oz. spirits) or prescription/illicit drug abuse..
• Have positive results on the urine drug screen or alcohol breath test indicative of illicit drug or alcohol abuse.
• Have a history or evidence of orthostatic hypotension.
• Have a resting heart rate of <50 beats per minutes or systolic blood pressure <100mmHg.
• Have been receiving or have received chronic opioid therapy defined as greater than 15 morphine equivalents units per day for greater than 3 out of 7 days per week over a one-month period within 12 months.
• Use concurrent therapy that could interfere with the evaluation of efficacy or safety, such as any drugs which in the investigator's opinion may exert significant analgesic properties or act synergistically with DEX-IN.
• Unable to discontinue medications, that have not been at a stable dose for at least 14 days prior to the scheduled bunionectomy procedure, within 5 half lives of the specific prior medication (or, if half life is not known, within 48 hours) before dosing.
• Have utilized any intranasal medications within the preceding 10 days.
• Have signs or a history of significant rhinitis or rhinorrhea (constant or chronic), nasal polyps, mucosal lesions of the nostril, postnasal drip of any etiology (constant or chronic), nasal ulcers, septal perforation or deviation, any nasal surgery, anosmia, nasal piercings, or frequent nosebleeds or other nasal pathology, that is sufficient to interfere with IN drug delivery.
• Have had an upper respiratory tract infection within 14 days of screening.
• Have utilized corticosteroids, either systemically, inhalational either intranasally or oral, or by intra-articular injection, within 14 days prior to the study.
• Have received any investigational product within 30 days before dosing with study medication.
• Have previously received DEX-IN in clinical trials, or had bunionectomy in the last 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DEX-IN 50mcg; DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours.	Drug: Intranasal Dexmedetomidine; Other Names: DEX-IN
Placebo Comparator: IN Placebo; IN Placebo every 6 hours for 48 hours.	Drug: Intranasal Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summed Pain Intensity Difference Over the First 48 Hours (SPID48).	Pain intensity was recorded using a Numeric Pain Rating Scale (Range 0-10) where 0 equates to no pain (better), and 10 equates to the worst pain imaginable (worse). Pain intensity scores were to be recorded at the following time points: 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours post Dose 1. Thereafter pain assessments were to be recorded every 2 hours until 48 hours post Dose 1. Pain intensity differences from baseline were calculated at each time point and a time weighted summed pain intensity difference (SPID) was then calculated. Time weighted SPID calculations were computed by multiplying a weight factor to each score prior to summation. The weight factor at each time point was the time elapsed since the previous observation.	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SPID at Various Other Time Points	Pain intensity was recorded using a Numeric Pain Rating Scale (Range 0-10) where 0 equates to no pain (better), and 10 equates to the worst pain imaginable (worse). Pain intensity scores were to be recorded at the following time points: 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours post Dose 1. Thereafter pain assessments were to be recorded every 2 hours until 48 hours post Dose 1. Pain intensity differences from baseline were calculated at each time point and a time weighted summed pain intensity difference (SPID) was then calculated. Time weighted SPID calculations were computed by multiplying a weight factor to each score prior to summation. The weight factor at each time point was the time elapsed since the previous observation.	Up to 48 Hours
Time to Perceptible and Meaningful Pain Relief	Kaplan-Meier analysis of time to perceptible and meaningful pain relief for 50th percentile of subjects. Time to perceptible pain relief and time to meaningful pain relief were measured using the double-stopwatch method. The first stopwatch was given to each subject with the instructions to stop the watch when they first perceive pain relief to occur (time to perceptible relief). Once the first watch was stopped, the second stopwatch was given to the subject with the instructions to stop the watch when they are first experiencing meaningful pain relief (time to meaningful relief). A shorter time to pain relief is better.	6 hours
Number of Subjects With Significant Pain Improvement Following the First Study Dose.		6 hours
Use of Rescue Medication (Oral Opioids)	Number of subjects requiring rescue medication (Oral opioids) within 48 hours after first study dose	48 hours
Time to First Rescue Medication Use	Kaplan Meier analysis of time to first use of rescue analgesia 50th percentile of subjects. Rescue analgesia (oral oxycodone) was available to subjects with inadequately controlled pain. All doses of rescue analgesia administered were recorded and the time from the first study dose to first rescue analgesia in each subject was evaluated. A longer time to first rescue is better.	48 hours
Number of Subjects With Complete Protection From PONV		24 hours

Collaborators and Investigators

• Sponsor: Baudax Bio
• Collaborators: Lotus Clinical Research, LLC

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: November 3, 2014
• First Submitted That Met QC Criteria: November 4, 2014
• First Posted (Estimate): November 5, 2014

Study Record Updates

• Last Update Posted (Actual): May 2, 2017
• Last Update Submitted That Met QC Criteria: March 21, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Pain; Analgesia; intranasal; dexmedetomidine; Bunionectomy; Bunion
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: REC-14-013