Trial Outcomes & Findings for Evaluation Of Efficacy And Safety Of Norspan In Moderate To Severe Pain Due To Osteoarthritis, Rheumatoid Arthritis, Joint/Muscle Pain (NCT NCT01961271)

NCT ID: NCT01961271

Last Updated: 2016-09-23

Results Overview

The primary efficacy outcome analysis is the pre- and post-intervention change in BS-11 pain score. The reduction in scores were calculated by subtracting the post-intervention score from the baseline score. BS-11 is known as "Box scale-11"; it is an 11-point scale measuring pain intensity. It ranges from 0 to 10, whereby 0 represents no pain and 10 represents the worst imaginable pain. Subjects selected a number based on the pain intensity they were feeling at that time.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

114 participants

Primary outcome timeframe

Maximum 17 weeks starting from enrolment

Results posted on

2016-09-23

Participant Flow

Participant milestones

Participant milestones
Measure	Buprenorphine Transdermal Patch Subjects will be on either 5mg, 10mg, 15mg, 20mg, 25mg, 30mg or 40mg doses for 17 weeks. Dose titration will occur every week for the first 6 weeks, and will be maintained for the next 11 weeks. Buprenorphine transdermal patch: Please see Arm Description.
Overall Study STARTED	114
Overall Study COMPLETED	64
Overall Study NOT COMPLETED	50

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluation Of Efficacy And Safety Of Norspan In Moderate To Severe Pain Due To Osteoarthritis, Rheumatoid Arthritis, Joint/Muscle Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Buprenorphine Transdermal Patch n=114 Participants Subjects will be on either 5mg, 10mg, 15mg, 20mg, 25mg, 30mg or 40mg doses for 17 weeks. Dose titration will occur every week for the first 6 weeks, and will be maintained for the next 11 weeks. Buprenorphine transdermal patch: Please see Arm Description.
Age, Continuous	57 years STANDARD_DEVIATION 13.4 • n=5 Participants
Sex: Female, Male Female	86 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants
Region of Enrollment Hong Kong	26 participants n=5 Participants
Region of Enrollment Philippines	26 participants n=5 Participants
Region of Enrollment Korea, Republic of	62 participants n=5 Participants

PRIMARY outcome

Timeframe: Maximum 17 weeks starting from enrolment

Population: Subjects of the analysis population met the eligibility criteria. It consists of subjects who completed the study and who withdrew for any reason.

Outcome measures

Outcome measures
Measure	Buprenorphine Transdermal Patch n=114 Participants Subjects will be on either 5mg, 10mg, 15mg, 20mg, 25mg, 30mg or 40mg doses for 17 weeks. Dose titration will occur every week for the first 6 weeks, and will be maintained for the next 11 weeks. Buprenorphine transdermal patch: Please see Arm Description.
Efficacy According to BS-11 Pain Score Reduction	2.7 units on a scale Standard Deviation 2.4

SECONDARY outcome

Timeframe: approximately 17 weeks starting from enrolment

Pre-intervention: Visit 1 Post-intervention: Visit 6 There are 5 dimensions in the EQ5D-3L questionnaire answered by the subjects, classified into 5 categories here: Mobility -- change in % of subjects who have no problem in walking around Self-care -- change in % of subjects who have no problem in self-care Usual activities -- change in % of subjects who have no problem with performing their usual activities Pain/ discomfort -- change in % of subjects who do not experience pain or discomfort Anxiety/ depression -- change in % of subjects who do not feel anxious or depressed

Outcome measures

Outcome measures
Measure	Buprenorphine Transdermal Patch n=114 Participants Subjects will be on either 5mg, 10mg, 15mg, 20mg, 25mg, 30mg or 40mg doses for 17 weeks. Dose titration will occur every week for the first 6 weeks, and will be maintained for the next 11 weeks. Buprenorphine transdermal patch: Please see Arm Description.
Secondary Efficacy Outcome Determined by Change in Percentage of Subjects Who Met Criteria on EQ5D-3L Quality of Life Questionnaire From Pre- to Post-intervention Mobility	25.8 percentage of subjects
Secondary Efficacy Outcome Determined by Change in Percentage of Subjects Who Met Criteria on EQ5D-3L Quality of Life Questionnaire From Pre- to Post-intervention Self-care	20.2 percentage of subjects
Secondary Efficacy Outcome Determined by Change in Percentage of Subjects Who Met Criteria on EQ5D-3L Quality of Life Questionnaire From Pre- to Post-intervention Anxiety/ Depression	18 percentage of subjects
Secondary Efficacy Outcome Determined by Change in Percentage of Subjects Who Met Criteria on EQ5D-3L Quality of Life Questionnaire From Pre- to Post-intervention Usual Activities	19.4 percentage of subjects
Secondary Efficacy Outcome Determined by Change in Percentage of Subjects Who Met Criteria on EQ5D-3L Quality of Life Questionnaire From Pre- to Post-intervention Pain/Discomfort	14.3 percentage of subjects

SECONDARY outcome

Timeframe: From time of enrolment up to 7 days after completion / discontinuation visit (up to 140 days)

Side effects of the transdermal patch treatment will be analysed.

Outcome measures

Outcome measures
Measure	Buprenorphine Transdermal Patch n=114 Participants Subjects will be on either 5mg, 10mg, 15mg, 20mg, 25mg, 30mg or 40mg doses for 17 weeks. Dose titration will occur every week for the first 6 weeks, and will be maintained for the next 11 weeks. Buprenorphine transdermal patch: Please see Arm Description.
Treatment-emergent Adverse Events (TEAE's) as Measured by Number of Subjects With at Least 1 TEAE	89 participants

SECONDARY outcome

Timeframe: Approximately 17 weeks starting from enrolment

Daily use of breakthrough pain medication from visits 1-6, assessed from patient diaries.

Outcome measures

Outcome measures
Measure	Buprenorphine Transdermal Patch n=114 Participants Subjects will be on either 5mg, 10mg, 15mg, 20mg, 25mg, 30mg or 40mg doses for 17 weeks. Dose titration will occur every week for the first 6 weeks, and will be maintained for the next 11 weeks. Buprenorphine transdermal patch: Please see Arm Description.
Secondary Efficacy Outcome as Measured by Number of Subjects Requiring at Least 1 Breakthrough (Rescue) Pain Medication	26 participants

SECONDARY outcome

Timeframe: At visit 6 (anywhere between Day 91 to 119 after enrolment depending on how long titration took)

The overall assessment of the change in pain intensity from baseline is measured at Visit 6. Physician's Global Impression of Change scale: Investigator's opinion on a scale of 1 to 7 where 1 is "very much improved" and 7 is "very much worse" Patient's Global Impression of Change scale: Subject's opinion on a scale of 1 to 7 where 1 is "very much improved" and 7 is "very much worse"

Outcome measures

Outcome measures
Measure	Buprenorphine Transdermal Patch n=114 Participants Subjects will be on either 5mg, 10mg, 15mg, 20mg, 25mg, 30mg or 40mg doses for 17 weeks. Dose titration will occur every week for the first 6 weeks, and will be maintained for the next 11 weeks. Buprenorphine transdermal patch: Please see Arm Description.
Secondary Efficacy Outcome on Physicians' and Patients' Treatment Satisfaction Assessed Using Physician's Global Impression of Change Scale and Patient's Global Impression of Change Scale Respectively Physician Impression	2.62 units on a scale Standard Deviation 0.84
Secondary Efficacy Outcome on Physicians' and Patients' Treatment Satisfaction Assessed Using Physician's Global Impression of Change Scale and Patient's Global Impression of Change Scale Respectively Patient Impression	2.66 units on a scale Standard Deviation 0.81

SECONDARY outcome

Timeframe: From time of enrolment to Visit 6 (ie. up to119 days from enrolment)

Outcome measures

Outcome measures
Measure	Buprenorphine Transdermal Patch n=114 Participants Subjects will be on either 5mg, 10mg, 15mg, 20mg, 25mg, 30mg or 40mg doses for 17 weeks. Dose titration will occur every week for the first 6 weeks, and will be maintained for the next 11 weeks. Buprenorphine transdermal patch: Please see Arm Description.
Secondary Efficacy Outcome -- Incidence of Early Treatment Discontinuation Due to Lack of Efficacy.	3 participants

Adverse Events

Buprenorphine Transdermal Patch

Serious events: 1 serious events

Other events: 89 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Buprenorphine Transdermal Patch n=114 participants at risk Subjects will be on either 5mg, 10mg, 15mg, 20mg, 25mg, 30mg or 40mg doses for 17 weeks. Dose titration will occur every week for the first 6 weeks, and will be maintained for the next 11 weeks. Buprenorphine transdermal patch: Please see Arm Description.
Cardiac disorders Hypertensive Crisis	0.88% 1/114 • Number of events 1 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.

Other adverse events

Other adverse events
Measure	Buprenorphine Transdermal Patch n=114 participants at risk Subjects will be on either 5mg, 10mg, 15mg, 20mg, 25mg, 30mg or 40mg doses for 17 weeks. Dose titration will occur every week for the first 6 weeks, and will be maintained for the next 11 weeks. Buprenorphine transdermal patch: Please see Arm Description.
Cardiac disorders Atrial Tachycardia	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Ear and labyrinth disorders Tinnitus	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Ear and labyrinth disorders Vertigo	1.8% 2/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Abdominal Discomfort	1.8% 2/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Abdominal Pain	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Constipation	31.6% 36/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Diarrhea	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Dry Mouth	1.8% 2/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Dyspepsia	1.8% 2/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Enteritis	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Eructation	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Flatulence	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Gingival Ulceration	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Nausea	39.5% 45/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Periodontitis	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Toothache	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Gastrointestinal disorders Vomiting	16.7% 19/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Application Site Erythema	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Application Site Irritation	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Application Site Pruritus	4.4% 5/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Application Site Rash	1.8% 2/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Application Site Swelling	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Application Site Warmth	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Asthenia	1.8% 2/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Chest Discomfort	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Chest Pain	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Fatigue	2.6% 3/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Feeling Cold	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Influenza-like Illness	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Edema	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
General disorders Pyrexia	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Immune system disorders Allergy to Arthropod Sting	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Infections and infestations Acute Tonsillitis	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Infections and infestations Nasopharyngitis	3.5% 4/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Infections and infestations Paronychia	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Infections and infestations Rhinitis	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Infections and infestations Upper Respiratory Tract Infection	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Infections and infestations Vaginal Infection	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Injury, poisoning and procedural complications Excoriation	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Injury, poisoning and procedural complications Muscle Injury	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Injury, poisoning and procedural complications Muscle Strain	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Investigations Alanine Aminotransferase Increased	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Metabolism and nutrition disorders Decreased Appetite	2.6% 3/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Musculoskeletal and connective tissue disorders Arthralgia	1.8% 2/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Musculoskeletal and connective tissue disorders Back Pain	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Musculoskeletal and connective tissue disorders Joint Effusion	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Musculoskeletal and connective tissue disorders Joint Swelling	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Musculoskeletal and connective tissue disorders Muscular Weakness	1.8% 2/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Musculoskeletal and connective tissue disorders Pain In Extremity	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Musculoskeletal and connective tissue disorders Synovial cyst	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Nervous system disorders Dizziness	27.2% 31/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Nervous system disorders Headache	8.8% 10/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Nervous system disorders Hypoesthesia	1.8% 2/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Nervous system disorders Somnolence	19.3% 22/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Psychiatric disorders Insomnia	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Renal and urinary disorders Dysuria	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Renal and urinary disorders Urinary Hesitation	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Respiratory, thoracic and mediastinal disorders Cough	1.8% 2/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.6% 3/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Skin and subcutaneous tissue disorders Cold Sweat	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Skin and subcutaneous tissue disorders Dermatitis Allergic	2.6% 3/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Skin and subcutaneous tissue disorders Erythema	1.8% 2/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.8% 2/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Skin and subcutaneous tissue disorders Pruritus	7.9% 9/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Skin and subcutaneous tissue disorders Rash	2.6% 3/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Skin and subcutaneous tissue disorders Urticaria	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.
Vascular disorders Hypertensive Crisis	0.88% 1/114 • The timeframe is up to 140 days. All adverse events will be recorded from the time the ICF is signed until 7 days after the completion/ discontinuation visit.

Additional Information

Valerie Anne Leck

Mundipharma Pte Ltd

Phone: +65 6511 1165

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Data emerging from the study cannot be released without the permission of the sponsor.
Publication restrictions are in place

Restriction type: OTHER