Pain, Post-operative
Conditions
Keywords
Bunion, Bunionectomy, Pain, Analgesia, dexmedetomidine, intranasal
Brief summary
The primary objective of this study is to evaluate the analgesic efficacy of two dose levels 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.
Interventions
DRUGIntranasal Dexmedetomidine
OTHERIntranasal Placebo
Sponsors
Lotus Clinical Research, LLC
Baudax Bio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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 DEX-IN/placebo or to any peri- or postoperative medications used in this study. * Have a clinically significant abnormal clinical laboratory tests 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summed Pain Intensity Difference Over the First 48 Hours (SPID48). | 48 hours | Pain intensity was recorded using a Numeric Rating Scale (Range 0-10) where 0 equates to no pain, and 10 equates to the worst pain imaginable. 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. Pain intensity differences from baseline at each time point were calculated and a time weighted 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DEX-IN 35mcg DEX-IN 35mcg every 6 hours for 48 hours. DEX-IN 35mcg PRN for up to 3 additional days.
Intranasal Dexmedetomidine | 31 |
| DEX-IN 50mcg DEX-IN 50mcg every 6 hours for 48 hours. DEX-IN 50mcg PRN for up to 3 additional days.
Intranasal Dexmedetomidine | 32 |
| IN Placebo IN Placebo every 6 hours for 48 hours. IN Placebo PRN for up to 3 additional days.
Intranasal Placebo | 32 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 1 |
| Overall Study | Lack of Efficacy | 1 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Subject declined to continue dosing | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | DEX-IN 35mcg | DEX-IN 50mcg | IN Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 43.6 years STANDARD_DEVIATION 14.53 | 44.6 years STANDARD_DEVIATION 12.21 | 44.6 years STANDARD_DEVIATION 13.93 | 44.2 years STANDARD_DEVIATION 13.44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 10 Participants | 14 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 22 Participants | 18 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 8 Participants | 11 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 24 Participants | 21 Participants | 69 Participants |
| Sex: Female, Male Female | 23 Participants | 28 Participants | 27 Participants | 78 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 5 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 28 / 31 | 30 / 32 | 26 / 32 |
| serious Total, serious adverse events | 0 / 31 | 0 / 32 | 0 / 32 |
Outcome results
Primary
Summed Pain Intensity Difference Over the First 48 Hours (SPID48).
Pain intensity was recorded using a Numeric Rating Scale (Range 0-10) where 0 equates to no pain, and 10 equates to the worst pain imaginable. 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. Pain intensity differences from baseline at each time point were calculated and a time weighted 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.
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DEX-IN 35mcg | Summed Pain Intensity Difference Over the First 48 Hours (SPID48). | 36.871 units on a scale | Standard Deviation 93.7979 |
| DEX-IN 50mcg | Summed Pain Intensity Difference Over the First 48 Hours (SPID48). | 44.719 units on a scale | Standard Deviation 79.059 |
| IN Placebo | Summed Pain Intensity Difference Over the First 48 Hours (SPID48). | 51.227 units on a scale | Standard Deviation 100.3288 |