NCT02310581

Buprenorphine Sublingual Spray for the Treatment of Moderate to Severe Pain

Terminated Phase 3 Results posted Last updated 9 August 2017

What this trial tests

Phase 3 trial testing Buprenorphine Sublingual Spray in Post-operative Pain in 40 participants. Terminated before completion.

Timeline

24 February 2015

Primary endpoint
19 March 2015

19 March 2015

Quick facts

Lead sponsor	INSYS Therapeutics Inc
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	40
Start date	24 February 2015
Primary completion	19 March 2015
Estimated completion	19 March 2015
Sites	3 locations across United States

Drugs / interventions tested

• Buprenorphine Sublingual Spray — full drug profile →
• Placebo

Conditions studied

• Post-operative Pain — all drugs for Post-operative Pain →

Sponsor

INSYS Therapeutics Inc — full company profile →

Who can join

Adults 18 to 65, any sex, with Post-operative Pain. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Numeric Rating Scale (NRS) Summed Pain Intensity Difference (SPID) Over 0 to 48 Hours After Time 0 (NRS SPID-48) Primary · Baseline and 0 to 48 hours after Time 0

Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points up to 48 hours after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain \[maximum

Group	Value	95% CI
Buprenorphine 0.5 mg TID	169.621	± 29.9942
Buprenorphine 1.0 mg BID	150.964	± 27.5418
Buprenorphine 1.0 mg TID	129.133	± 29.3429
Placebo	64.648	± 29.0597

NRS Mean Pain Intensity Difference (PID) at 4, 8, 24 and 48 Hours After Time 0 Secondary · Baseline and 4, 8, 24 and 48 hours after Time 0

Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug administration) and at multiple time points up to 48 hours after Time 0 (time of administration of the first dose of study drug). NRS PID is defined as the difference in pain at each scheduled timepoint relative to Baseline (PID=pain intensity at baseline - pain intensity at time point). A higher value of NRS PID score indicates a higher decrease in pain from Baseline.

4 Hours

Group	Value	95% CI
Buprenorphine 0.5 mg TID	4.7	± 1.73
Buprenorphine 1.0 mg BID	3.4	± 3.01
Buprenorphine 1.0 mg TID	3.8	± 2.94
Placebo	1.6	± 1.33

8 Hours

Group	Value	95% CI
Buprenorphine 0.5 mg TID	3.4	± 1.41
Buprenorphine 1.0 mg BID	4.0	± 2.97
Buprenorphine 1.0 mg TID	3.9	± 2.28
Placebo	1.2	± 1.99

24 Hours

Group	Value	95% CI
Buprenorphine 0.5 mg TID	5.5	± 1.76
Buprenorphine 1.0 mg BID	3.0	± 3.16
Buprenorphine 1.0 mg TID	3.4	± 1.81
Placebo	2.6	± 1.94

48 Hours

Group	Value	95% CI
Buprenorphine 0.5 mg TID	6.3	± 1.03
Buprenorphine 1.0 mg BID	4.2	± 2.39
Buprenorphine 1.0 mg TID	4.1	± 2.80
Placebo	3.2	± 2.64

NRS Mean Pain Intensity Score at 4, 8, 24 and 48 Hours After Time 0 Secondary · 4, 8, 24 and 48 hours after Time 0

Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug administration) and at multiple time points up to 48 hours after Time 0 (time of administration of the first dose of study drug). A lower value indicates improvement in pain.

4 Hours

Group	Value	95% CI
Buprenorphine 0.5 mg TID	2.2	± 2.49
Buprenorphine 1.0 mg BID	2.9	± 3.08
Buprenorphine 1.0 mg TID	4.0	± 2.87
Placebo	4.9	± 3.14

8 Hours

Group	Value	95% CI
Buprenorphine 0.5 mg TID	3.5	± 2.14
Buprenorphine 1.0 mg BID	2.3	± 3.00
Buprenorphine 1.0 mg TID	3.9	± 2.42
Placebo	5.2	± 2.64

24 Hours

Group	Value	95% CI
Buprenorphine 0.5 mg TID	1.8	± 1.47
Buprenorphine 1.0 mg BID	3.3	± 2.55
Buprenorphine 1.0 mg TID	4.6	± 2.07
Placebo	3.9	± 2.80

48 Hours

Group	Value	95% CI
Buprenorphine 0.5 mg TID	1.0	± 0.89
Buprenorphine 1.0 mg BID	2.1	± 1.76
Buprenorphine 1.0 mg TID	3.9	± 2.42
Placebo	3.2	± 2.11

NRS SPID Over 0 to 4 Hours After Time 0 (NRS SPID-4) Secondary · Baseline and 0 to 4 hours after Time 0

Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points up to 4 hours after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain \[maximum

Group	Value	95% CI
Buprenorphine 0.5 mg TID	11.430	± 3.6221
Buprenorphine 1.0 mg BID	5.088	± 3.3259
Buprenorphine 1.0 mg TID	7.095	± 3.5434
Placebo	-2.968	± 3.5092

NRS SPID Over 0 to 8 Hours After Time 0 (NRS SPID-8) Secondary · Baseline and 0 to 8 hours after Time 0

Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points up to 8 hours after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain \[maximum

Group	Value	95% CI
Buprenorphine 0.5 mg TID	24.283	± 6.2667
Buprenorphine 1.0 mg BID	19.223	± 5.7543
Buprenorphine 1.0 mg TID	19.761	± 6.1306
Placebo	-2.382	± 6.0715

NRS SPID Over 0 to 24 Hours After Time 0 (NRS SPID-24) Secondary · Baseline and 0 to 24 hours after Time 0

Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points up to 24 hours after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain \[maximum

Group	Value	95% CI
Buprenorphine 0.5 mg TID	83.668	± 14.0612
Buprenorphine 1.0 mg BID	70.071	± 12.9115
Buprenorphine 1.0 mg TID	76.666	± 13.7558
Placebo	19.787	± 13.6231

Percentage of Participants Who Used Rescue Medication for Pain Secondary · From Time 0 (first dose of study drug) up to Day 9

The percentage of participants who needed to take an alternate medication for pain relief during the study.

Group	Value	95% CI
Buprenorphine 0.5 mg TID	44.4
Buprenorphine 1.0 mg BID	54.5
Buprenorphine 1.0 mg TID	60.0
Placebo	100

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious Adverse Events: from signing of informed consent to the Follow-up visit (up to 9 days). Non-serious Adverse Events: from the first dose of study drug to the Follow-up visit (up to 9 days).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Buprenorphine 0.5 mg TID

Serious: 1/9 (11%)

Deaths: —

Buprenorphine 1.0 mg BID

Serious: 0/11 (0%)

Deaths: —

Buprenorphine 1.0 mg TID

Serious: 0/10 (0%)

Deaths: —

Placebo

Serious: 0/10 (0%)

Deaths: —

Serious adverse events (1 terms)

Reaction	System	Buprenorphine 0.5 mg TID	Buprenorphine 1.0 mg BID	Buprenorphine 1.0 mg TID	Placebo
Atrial fibrillation	Cardiac disorders	—	—	—	—

Other adverse events (56 terms — click to expand)

Reaction	System	Buprenorphine 0.5 mg TID	Buprenorphine 1.0 mg BID	Buprenorphine 1.0 mg TID	Placebo
Nausea	Gastrointestinal disorders	—	—	—	—
Emesis	Gastrointestinal disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Drowsiness	Nervous system disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Xerostomia	Gastrointestinal disorders	—	—	—	—
Incision site erythema	Injury, poisoning and procedural complications	—	—	—	—
Intermittent headache	Nervous system disorders	—	—	—	—
Lightheadedness	Nervous system disorders	—	—	—	—
Diaphoresis	Skin and subcutaneous tissue disorders	—	—	—	—
Hot flush	Vascular disorders	—	—	—	—
Visual disturbance	Eye disorders	—	—	—	—
Burning mouth	Gastrointestinal disorders	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—
Heartburn	Gastrointestinal disorders	—	—	—	—
Loose stools	Gastrointestinal disorders	—	—	—	—
Numbness mouth	Gastrointestinal disorders	—	—	—	—
Sore mouth	Gastrointestinal disorders	—	—	—	—
Tingling lips	Gastrointestinal disorders	—	—	—	—
Tingling tongue	Gastrointestinal disorders	—	—	—	—
Feeling hot	General disorders	—	—	—	—
Shivering	General disorders	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—
Post procedural cellulitis	Infections and infestations	—	—	—	—
Oxygen saturation decreased	Investigations	—	—	—	—
Respiratory rate decreased	Investigations	—	—	—	—
Temperature elevation	Investigations	—	—	—	—
Anorexia	Metabolism and nutrition disorders	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—
Cramps in leg	Musculoskeletal and connective tissue disorders	—	—	—	—
Low back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Dizzy	Nervous system disorders	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—
Paresthesia of fingers	Nervous system disorders	—	—	—	—
Shakiness	Nervous system disorders	—	—	—	—
Trembling	Nervous system disorders	—	—	—	—

Most-reported serious reactions: Atrial fibrillation.

Data from ClinicalTrials.gov NCT02310581 adverse events section.

Sponsor's own description

This is a phase 3, multicenter, randomized, double-blind, multiple-dose, parallel-group, placebo-controlled study to evaluate the safety and efficacy of up to 3 dosing regimens of Buprenorphine Sublingual (under the tongue) Spray and/or matching placebo in participants with moderate to severe postoperative pain after bunionectomy. The study will comprise 4 periods: the Screening Period, the Surgical Period, the Treatment Period, and the Follow-up Period.

Participants will be admitted to the study site on the morning of the scheduled surgery, will remain at the study site until postoperative Day 3 (a total of 3 nights at the study site), and will return for the Follow-up Visit 5 to 9 days after surgery.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.