Clinical trial NCT03254459: Study of Buprenorphine Sublingual Spray Versus Standard of Care Narcotic Therapy for the Treatment of Post-Operative Pain
Official title: A Phase 2, Randomized, Open Label, Multiple-Dose, Comparator, Parallel-Group, Safety and Tolerance Study of Buprenorphine Sublingual Spray (0.5 mg TID) Versus Standard of Care Post-Operative Narcotic Therapy for the Treatment of Post-Operative Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pain, Postoperative
Lead sponsor: INSYS Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2017-08-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety and tolerability based on the incidence of adverse experiences of buprenorphine sublingual spray (0.5 milligrams \[mg\] three times daily \[TID\]) compared with standard post-operative narcotic therapy in participants with postoperative pain. Standard post-operative narcotic therapy is defined as morphine intravenous (IV) injection (4 mg TID) followed by oxycodone hydrochloride tablet (10 mg TID).


Eligibility criteria: Inclusion criteria:

1. Is able to speak and understand the language in which the study is being conducted, is able to understand and comply with the procedures and study requirements, and has voluntarily signed and dated an informed consent form approved by an Institutional Review Board before the conduct of any study procedure.
2. Is a male or female ≥18 and ≤65 years of age.
3. Scheduled for elective bunionectomy, breast augmentation (in women only), or abdominoplasty.
4. Is classified using the American Society of Anesthesiologists Physical Status Classification System as P1 to P2.
5. If female, is either not of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile \[bilateral tubal ligation, bilateral oophorectomy, or hysterectomy\]) or practicing one of the following medically acceptable methods of birth control:

   1. Hormonal methods such as oral, implantable, injectable, vaginal ring, or transdermal contraceptives for a minimum of 1 full cycle (based on the participant's usual menstrual cycle period) before study drug administration;
   2. Total abstinence from sexual intercourse since the last menses before study drug administration;
   3. Intrauterine device; OR
   4. Double-barrier method (condoms, sponge, or diaphragm with spermicidal jellies or cream).
6. Has a body weight ≥45 kilograms (kg) and a body mass index (BMI) ≤40 kg/m\^2.
7. Is willing and able to comply with study requirements (including diet, alcohol, and smoking restrictions), complete evaluations and diary, remain at the study site for ≥72 hours, and return for follow up Day 8 + 2 days after surgery.

Exclusion criteria:

1. Has a known history of allergic reaction or clinically significant intolerance to acetaminophen, aspirin, opioids, or any nonsteroidal anti-inflammatory drugs (NSAIDs); history of NSAID-induced bronchospasm (participants with the triad of asthma, nasal polyps, and chronic rhinitis are at greater risk for bronchospasm and should be considered carefully); or hypersensitivity, allergy, or significant reaction to sulfa (including sulfonamide) medicines, ingredients of the study drug, or any other drugs used in the study, including anesthetics and antibiotics that may be required on the day of surgery.
2. Has experienced any surgical complications or other issues that, in the investigator's opinion, could compromise the participant's safety if he or she continues into randomized treatment or could confound the results of the study.
3. Has a known or suspected history of alcoholism or drug abuse or misuse within 2 years of Screening or evidence of opioid tolerance or physical dependence before dosing with the study drug.
4. Has any clinically significant unstable cardiac, respiratory, neurological, immunological, hematological, or renal disease, or any other condition that, in the investigator's opinion, could compromise the participant's welfare, ability to communicate with the study staff, or otherwise contraindicate study participation.
5. Has long QT Syndrome, a family history of long QT Syndrome, or is taking Class IA or Class III antiarrhythmic medications
6. Has a history or current diagnosis of a significant psychiatric disorder that, in the investigator's opinion, would affect the participant's ability to comply with the study requirements.
7. Has tested positive either on the urine drug screen or on the alcohol Breathalyzer test. Participants who test positive at Screening only and can produce a prescription in their name from their physician for the medication producing the positive test may be considered for study enrollment at the investigator's discretion. However, they must test negative on the day of the surgery.
8. Has a history of a clinically significant (in the investigator's opinion) gastrointestinal (GI) event within 6 months before Screening or has any history of peptic or gastric ulcers or GI bleeding.
9. Has an active infection, mucositis, cold sores, viral lesions, local irritation, or in the investigator's opinion has significant periodontal disease of the oral cavity. In addition, recent (within 1 year) piercing of the tongue or anywhere in the oral cavity.
10. Has a surgical or medical condition of the GI or renal system that, in the investigator's opinion, might significantly alter the absorption, distribution, or excretion of any drug substance.
11. Is considered by the investigator, for any reason (including, but not limited to, the risks described as precautions, warnings, and contraindications in the current version of the investigator's brochure for Buprenorphine Sublingual Spray), to be an unsuitable candidate to receive the study drug.
12. Is receiving systemic chemotherapy, has an active malignancy of any type, or has been diagnosed with cancer within 5 years before Screening (excluding squamous or basal cell carcinoma of the skin).
13. Is currently receiving anticoagulants (eg, heparin or warfarin). Low-dose aspirin for cardioprotection is allowed.
14. Has used drugs known to be a strong inhibitor or inducer of CYP3A4 within 1 week before surgery.
15. Has received a course of systemic corticosteroids (either oral or parenteral) within 1 month before Screening (inhaled nasal steroids and topical corticosteroids are allowed).
16. Has a history of chronic use (defined as daily use for \>2 weeks) of NSAIDs, opiates, or glucocorticoids (except inhaled nasal steroids and topical corticosteroids) within 1 month before study drug administration. Aspirin at a daily dose of ≤325 mg is allowed for cardiovascular prophylaxis if the participant has been on a stable dose regimen for ≥30 days before Screening and has not experienced any relevant medical problem.
17. Has a significant renal or hepatic disease, as indicated by clinical laboratory assessment (results ≥3 × the upper limit of normal \[ULN\] for any liver function test, including aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, or creatinine ≥1.5 × ULN).
18. Has any clinically significant laboratory or 12-lead electrocardiogram finding at Screening that in the investigator's opinion contraindicates study participation.
19. Has screening systolic blood pressure ≥160 mmHg and diastolic blood pressure \>100 mmHg (may be repeated one additional time after 5 minutes rest to verify). The investigator may, at his discretion, choose to exclude participants with hypertensive levels lower than these if he deems it in the best interest of the participant.
20. Has a history of sleep apnea or other obstructive airway disease.
21. Has a history of nausea and vomiting with buprenorphine products.
22. Has significant difficulties swallowing capsules or is unable to tolerate oral medication.
23. Previously participated in another clinical study of Buprenorphine Sublingual Spray or received any investigational drug or device or investigational therapy within 30 days before Screening.

Post-surgical eligibility requirements:

The participant will be assessed for the following postoperative eligibility criteria

1. Participants must be awake, breathing spontaneously without significant respiratory depression.
2. Participants must not be actively vomiting or complaining of severe nausea.
3. Participants must be able to answer questions and follow commands.
4. Participants must not have surgical complications that could compromise safety of the participant or confound the results of the study.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Days 1 to 8
Secondary outcomes:
measure: Percentage of Participants Provided Rescue Medication for Nausea
timeFrame: Days 1 to7
measure: Time to First Use of Rescue Medication for Nausea Following Each Dose of the Investigational Product (IP)
timeFrame: Days 1 to 7
measure: Total Use of Rescue Medication for Nausea Over 0 to 24 Hours, Over 0 to 48 Hours, Over 0-72 Hours and 0-7 Days
timeFrame: 0 to 24 hours, 0 to 48 hours, 0 to 72 hours and 0 to 7 days
measure: Pulse Oximetry Levels at 90 Minutes,12, 24, 48 and 72 Hours
timeFrame: 90 Minutes,12, 24, 48 and 72 Hours
measure: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings at 90 Minutes,12, 24, 48 and 72 Hours
timeFrame: Pre-dose and 90 minutes, 12, 24, 48 and 72 hours after first dose
measure: Number of Participants With Abnormal Oral Cavity Examinations
timeFrame: Pre-dose and 90 minutes, 12, 24, 48 and 72 hours after first dose on Days 1 to 4 and End of Study Day 8
Other outcomes:
Locations:
city: Pasadena
country: United States
facility: Lotus Clinical Research, LLC
state: California
city: Murray
country: United States
facility: Epic Medical Research
state: Utah
Study officials:
affiliation: INSYS Therapeutics Inc
name: Giovanni DeCastro
role: STUDY_DIRECTOR
References: