Trial Outcomes & Findings for An Interventional Study to Assess the Efficacy and Safety of Buprenorphine in Korean Patients With Spinal Disorders (NCT NCT01818700)

Last Updated: 2015-10-22

Results Overview

NRS-Pain scale assessed the severity of a subject's lower back pain on a scale of 0 (No pain) and 10 (Worst possible pain). NRS-Pain scale: Change = mean score at Week 8/ET minus mean score at Baseline.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

245 participants

Primary outcome timeframe

8 weeks

Results posted on

2015-10-22

Participant Flow

Duration of study: from 16 Oct. 2012 to 28 Jun 2013

This study is single arm for Norspan(buprenorphine) patch. Treatment with NORSPAN will be started from 5 μg/h for 2 weeks, and proper titration(up-titration) will be allowed at visit 2(wk 2) and at visit 3(wk 4) according to the investigator's decision. judgement by considering any titration needed situation.

Participant milestones

Participant milestones
Measure	Single Arm - Norspan Patch (Buprenorphine) This study is single arm for Norspan(buprenorphine) patch. Treatment with NORSPAN Ò will be started from 5 μg/h (1 patch a week) for 2 weeks, and proper titration (up-titration) will be allowed at visit 2(wk 2) and at visit 3(wk 4) according to the investigator's decision. The up-titration will be considered by investigator's judgement as follows; (1) if the rescue medication was used more than 2 times per day, on average or (2) based on the daily average NRS(Numeric Rating Scale), if the NRS was changed to worsen since the previous visit, (3) Investigator's judgement by considering any titration needed situation (e.g. dose, frequency of rescue medication).
Overall Study STARTED	245
Overall Study Safety Set	241
Overall Study FAS Set	210
Overall Study PP Set	105
Overall Study COMPLETED	141
Overall Study NOT COMPLETED	104

Reasons for withdrawal

Reasons for withdrawal
Measure	Single Arm - Norspan Patch (Buprenorphine) This study is single arm for Norspan(buprenorphine) patch. Treatment with NORSPAN Ò will be started from 5 μg/h (1 patch a week) for 2 weeks, and proper titration (up-titration) will be allowed at visit 2(wk 2) and at visit 3(wk 4) according to the investigator's decision. The up-titration will be considered by investigator's judgement as follows; (1) if the rescue medication was used more than 2 times per day, on average or (2) based on the daily average NRS(Numeric Rating Scale), if the NRS was changed to worsen since the previous visit, (3) Investigator's judgement by considering any titration needed situation (e.g. dose, frequency of rescue medication).
Overall Study Adverse Event	67
Overall Study Lack of Efficacy	2
Overall Study Lost to Follow-up	5
Overall Study Withdrawal by Subject	27
Overall Study Protocol Violation	2
Overall Study Other	1

Baseline Characteristics

An Interventional Study to Assess the Efficacy and Safety of Buprenorphine in Korean Patients With Spinal Disorders

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Norspan Patch (Buprenorphine) n=241 Participants Trade name is Norspan. Buprenorphine 5μg/h, 10 μg/h, 20 μg/h patches will be used (4 patches a box). Patch will be administered every 7th day. Buprenorphine: 8weeks treatment with Norspan®(Buprenorphine)
Age, Customized Age	63.51 years STANDARD_DEVIATION 11.53 • n=5 Participants
Sex: Female, Male Female	167 Participants n=5 Participants
Sex: Female, Male Male	74 Participants n=5 Participants
Region of Enrollment Korea, Republic of	241 participants n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: FAS set: 210. Missing values were imputed by LOCF FAS included the data obtained from all subjects who had at least one dose of the study drug and had data of at least one primary efficacy endpoint assessment.

Outcome measures

Outcome measures
Measure	Single Arm-Norspan Patch (Buprenorphine) n=210 Participants This study is single study with buprenorphine. Treatment with NORSPAN Ò will be started from 5 μg/h (1 patch a week) for 2 weeks, and proper titration (up-titration) will be allowed at visit 2(wk 2) and at visit 3(wk 4) according to the investigator's decision. The up-titration will be considered by investigator's judgement as follows; (1) if the rescue medication was used more than 2 times per day, on average or (2) based on the daily average NRS(Numeric Rating Scale), if the NRS was changed to worsen since the previous visit, (3) Investigator's judgement by considering any titration needed situation (e.g. dose, frequency of rescue medication).
Change of Pain Intensity* at Week 8 of Treatment With the Study Drug From Baseline	-1.65 units on a scale Standard Deviation 1.96

SECONDARY outcome

Timeframe: 4 weeks

Population: FAS set: 210. Missing values were imputed LOCF.

NRS-Pain scale assessed the severity of a subject's lower back pain on a scale of 0 (No pain) and 10 (Worst possible pain). NRS-Pain scale: Change = mean score at Week 4/ET minus mean score at Baseline.

Outcome measures

Outcome measures
Measure	Single Arm-Norspan Patch (Buprenorphine) n=210 Participants This study is single study with buprenorphine. Treatment with NORSPAN Ò will be started from 5 μg/h (1 patch a week) for 2 weeks, and proper titration (up-titration) will be allowed at visit 2(wk 2) and at visit 3(wk 4) according to the investigator's decision. The up-titration will be considered by investigator's judgement as follows; (1) if the rescue medication was used more than 2 times per day, on average or (2) based on the daily average NRS(Numeric Rating Scale), if the NRS was changed to worsen since the previous visit, (3) Investigator's judgement by considering any titration needed situation (e.g. dose, frequency of rescue medication).
Change of Pain Intensity at 4 Week of Treatment With Study Srug From Baseline.	-1.26 units on a scale Standard Deviation 1.71

SECONDARY outcome

Timeframe: 8 weeks

Population: FAS set: 210. Missing values were imputed by LOCF. Even though 210 subjects at Visit 1, baseline were assessed EQ-5D questionnaire, At visit 4(8weeks), 153 subjects were assessed EQ-5D questionnaire.

The Euroqol Health Survey (EQ-5D, 3-level) was completed on five dimensions (mobility, self care, usual activities, pain/discomfort and anxiety/depression) to measure health-related quality of life on a scale from 0-1. A higher score indicates better quality of life. EQ-5D score = 1 - 0.081 - (relevant score by level for the relevant item)-0.269 (only if there is at least one level 3). Table of scores by level for EQ-5D items mobility(level 1=0, level2=0.069,level 3=0.314), self care(level 1=0, level2=0.104,level 3=0.214), usual activities(level 1=0, level2=0.036,level 3=0.094), pain/discomfort (level 1=0, level2=0.,level 3=0.386) and anxiety/depression(level 1=0, level2=0.071,level 3=0.236).

Outcome measures

Outcome measures
Measure	Single Arm-Norspan Patch (Buprenorphine) n=153 Participants This study is single study with buprenorphine. Treatment with NORSPAN Ò will be started from 5 μg/h (1 patch a week) for 2 weeks, and proper titration (up-titration) will be allowed at visit 2(wk 2) and at visit 3(wk 4) according to the investigator's decision. The up-titration will be considered by investigator's judgement as follows; (1) if the rescue medication was used more than 2 times per day, on average or (2) based on the daily average NRS(Numeric Rating Scale), if the NRS was changed to worsen since the previous visit, (3) Investigator's judgement by considering any titration needed situation (e.g. dose, frequency of rescue medication).
Change in Quality of Life at 8 Week of Treatment With Study Drug From Baseline	0.18 units on a scale Standard Deviation 0.31

SECONDARY outcome

Timeframe: 8 week

Population: FAS set: 210. Missing values were imputed by LOCF. Even though 210 subjects were assessed EQ-VAS at visit 1(baseline), 153 Subjects were assessed EQ-VAS at visit 4(8week)

EQ-5D Visual Analogue Scale (VAS) in rates the participant's overall health status using values from 0 (worst imaginable) to 100 (best imaginable).

Outcome measures

Outcome measures
Measure	Single Arm-Norspan Patch (Buprenorphine) n=153 Participants This study is single study with buprenorphine. Treatment with NORSPAN Ò will be started from 5 μg/h (1 patch a week) for 2 weeks, and proper titration (up-titration) will be allowed at visit 2(wk 2) and at visit 3(wk 4) according to the investigator's decision. The up-titration will be considered by investigator's judgement as follows; (1) if the rescue medication was used more than 2 times per day, on average or (2) based on the daily average NRS(Numeric Rating Scale), if the NRS was changed to worsen since the previous visit, (3) Investigator's judgement by considering any titration needed situation (e.g. dose, frequency of rescue medication).
Change of EQ-VAS at 8 Weeks of Treatment With Study Drug From Baseline.	10.55 units on a scale Standard Deviation 24.76

SECONDARY outcome

Timeframe: 8weeks

Population: FAS set: 210. Missing values were imputed by LOCF.

Number of clinician with categorical change in overall status. CGIC: a clinician-rated instrument assessing change in clinician's overall status from baseline, on a scale ranging from 1 (very much improved) to 7 (very much worse).

Outcome measures

Outcome measures
Measure	Single Arm-Norspan Patch (Buprenorphine) n=210 Participants This study is single study with buprenorphine. Treatment with NORSPAN Ò will be started from 5 μg/h (1 patch a week) for 2 weeks, and proper titration (up-titration) will be allowed at visit 2(wk 2) and at visit 3(wk 4) according to the investigator's decision. The up-titration will be considered by investigator's judgement as follows; (1) if the rescue medication was used more than 2 times per day, on average or (2) based on the daily average NRS(Numeric Rating Scale), if the NRS was changed to worsen since the previous visit, (3) Investigator's judgement by considering any titration needed situation (e.g. dose, frequency of rescue medication).
Clinician Global Impression of Change(CGIC) Very much improved	16 participants
Clinician Global Impression of Change(CGIC) Much improved	63 participants
Clinician Global Impression of Change(CGIC) Minimally improved	55 participants
Clinician Global Impression of Change(CGIC) No change	68 participants
Clinician Global Impression of Change(CGIC) Minimally worse	8 participants
Clinician Global Impression of Change(CGIC) Much worse	0 participants
Clinician Global Impression of Change(CGIC) Very much worse	0 participants

SECONDARY outcome

Timeframe: 8 week

Population: FAS set: 210. Missing values were imputed by LOCF.

Number of clinician with categorical change in overall status. PGIC: a participant-rated instrument assessing change in patient's overall status from baseline, on a scale ranging from 1 (very much improved) to 7 (very much worse).

Outcome measures

Outcome measures
Measure	Single Arm-Norspan Patch (Buprenorphine) n=210 Participants This study is single study with buprenorphine. Treatment with NORSPAN Ò will be started from 5 μg/h (1 patch a week) for 2 weeks, and proper titration (up-titration) will be allowed at visit 2(wk 2) and at visit 3(wk 4) according to the investigator's decision. The up-titration will be considered by investigator's judgement as follows; (1) if the rescue medication was used more than 2 times per day, on average or (2) based on the daily average NRS(Numeric Rating Scale), if the NRS was changed to worsen since the previous visit, (3) Investigator's judgement by considering any titration needed situation (e.g. dose, frequency of rescue medication).
Patients Global Impression og Change(PGIC) Minimally worse	10 participants
Patients Global Impression og Change(PGIC) Much worse	0 participants
Patients Global Impression og Change(PGIC) Very much improved	12 participants
Patients Global Impression og Change(PGIC) Much improved	60 participants
Patients Global Impression og Change(PGIC) Minimally improved	57 participants
Patients Global Impression og Change(PGIC) No change	71 participants
Patients Global Impression og Change(PGIC) Very much worse	0 participants

Adverse Events

Norspan Patch (Buprenorphine)

Serious events: 1 serious events

Other events: 143 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Norspan Patch (Buprenorphine) n=241 participants at risk Trade name is Norspan. Buprenorphine 5μg/h, 10 μg/h, 20 μg/h patches will be used (4 patches a box). Patch will be administered every 7th day. Buprenorphine: 8weeks treatment with Norspan®(Buprenorphine)
Musculoskeletal and connective tissue disorders Lumbar vertebral fracture	0.41% 1/241 • Number of events 1 • 8 weeks

Other adverse events

Other adverse events
Measure	Norspan Patch (Buprenorphine) n=241 participants at risk Trade name is Norspan. Buprenorphine 5μg/h, 10 μg/h, 20 μg/h patches will be used (4 patches a box). Patch will be administered every 7th day. Buprenorphine: 8weeks treatment with Norspan®(Buprenorphine)
Gastrointestinal disorders Nausea	29.5% 71/241 • Number of events 77 • 8 weeks
Gastrointestinal disorders Vomiting	14.5% 35/241 • Number of events 36 • 8 weeks
Gastrointestinal disorders Constipation	2.9% 7/241 • Number of events 7 • 8 weeks
Gastrointestinal disorders Abdominal pain upper	1.2% 3/241 • Number of events 3 • 8 weeks
Gastrointestinal disorders Dry mouth	0.83% 2/241 • Number of events 2 • 8 weeks
Gastrointestinal disorders Dyspepsia	0.83% 2/241 • Number of events 2 • 8 weeks
Gastrointestinal disorders Abdominal discomfort	0.41% 1/241 • Number of events 1 • 8 weeks
Gastrointestinal disorders Diarrhoea	0.41% 1/241 • Number of events 1 • 8 weeks
Gastrointestinal disorders Lip swelling	0.41% 1/241 • Number of events 1 • 8 weeks
Nervous system disorders Dizziness	20.7% 50/241 • Number of events 52 • 8 weeks
Nervous system disorders Headache	5.8% 14/241 • Number of events 14 • 8 weeks
Nervous system disorders Somnolence	2.5% 6/241 • Number of events 7 • 8 weeks
Nervous system disorders Lethargy	0.83% 2/241 • Number of events 2 • 8 weeks
Nervous system disorders Paraesthesia	0.41% 1/241 • Number of events 1 • 8 weeks
Skin and subcutaneous tissue disorders Pruritus	9.1% 22/241 • Number of events 24 • 8 weeks
Skin and subcutaneous tissue disorders Erythema	0.83% 2/241 • Number of events 2 • 8 weeks
Skin and subcutaneous tissue disorders Blister	0.41% 1/241 • Number of events 1 • 8 weeks
Skin and subcutaneous tissue disorders Rash	0.41% 1/241 • Number of events 1 • 8 weeks
General disorders Chills	0.83% 2/241 • Number of events 2 • 8 weeks
General disorders Chest discomfort	0.41% 1/241 • Number of events 1 • 8 weeks
General disorders Cyst	0.41% 1/241 • Number of events 1 • 8 weeks
General disorders Face oedema	0.41% 1/241 • Number of events 1 • 8 weeks
General disorders Feeling hot	0.41% 1/241 • Number of events 1 • 8 weeks
General disorders General physical health deterioration	0.41% 1/241 • Number of events 1 • 8 weeks
General disorders Pain	0.41% 1/241 • Number of events 1 • 8 weeks
General disorders Thirst	0.41% 1/241 • Number of events 1 • 8 weeks
Psychiatric disorders Insomnia	1.2% 3/241 • Number of events 3 • 8 weeks
Psychiatric disorders Sleep disorder	0.83% 2/241 • Number of events 2 • 8 weeks
Psychiatric disorders Anxiety	0.41% 1/241 • Number of events 1 • 8 weeks
Metabolism and nutrition disorders Decreased appetite	0.83% 2/241 • Number of events 2 • 8 weeks
Metabolism and nutrition disorders Polydipsia	0.83% 2/241 • Number of events 2 • 8 weeks
Musculoskeletal and connective tissue disorders Muscular weakness	0.41% 1/241 • Number of events 1 • 8 weeks
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.41% 1/241 • Number of events 1 • 8 weeks
Musculoskeletal and connective tissue disorders Sensation of heaviness	0.41% 1/241 • Number of events 1 • 8 weeks
Cardiac disorders Palpitations	0.83% 2/241 • Number of events 2 • 8 weeks
Renal and urinary disorders Dysuria	0.83% 2/241 • Number of events 2 • 8 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.41% 1/241 • Number of events 1 • 8 weeks
Respiratory, thoracic and mediastinal disorders Productive cough	0.41% 1/241 • Number of events 1 • 8 weeks
Ear and labyrinth disorders Tinnitus	0.41% 1/241 • Number of events 1 • 8 weeks
Eye disorders Lacrimal disorder	0.41% 1/241 • Number of events 1 • 8 weeks
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.41% 1/241 • Number of events 1 • 8 weeks
Vascular disorders Flushing	0.41% 1/241 • Number of events 1 • 8 weeks

Additional Information

Dr. Whan Eoh

Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University school of medicine, Seoul Korea

Phone: 82-2-3410-3491

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place