Trial Outcomes & Findings for Buprenorphine Transdermal System (BTDS) in Subjects w/Mod-sev Osteoarthritis (OA) Chronic Pain of Knee (NCT NCT00531427)

Last Updated: 2012-09-10

Results Overview

"Average pain over the last 24 hours" scores of the study knee at week 12 was evaluated on an 11-point scale: 0 = no pain, 10 = worst pain imaginable, recorded daily.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

567 participants

Primary outcome timeframe

24 hours (week 12)

Results posted on

2012-09-10

Participant Flow

27-Sep-2007 (first patient first visit) to 28-Apr-2009 (last patient last visit) at 83 medical/research sites in US

Open-label run-in period designed to select those subjects who both tolerated and responded to treatment with BTDS 10 or BTDS 20 (an enriched design). N = 1151 entered the run-in period, and N = 571 completed. One subject was not dosed, therefore N = 570 randomized. N = 3 subjects did not have safety data, therefore N = 567 had double-blind data.

Participant milestones

Participant milestones
Measure	Double-blind BTDS 10 or 20 Buprenorphine transdermal patches (BTDS) 10 or 20 mcg/h applied for 7-day wear	Double-blind Placebo Placebo patches to match the BTDS patches applied for 7-day wear
Overall Study STARTED	282	285
Overall Study COMPLETED	209	191
Overall Study NOT COMPLETED	73	94

Reasons for withdrawal

Reasons for withdrawal
Measure	Double-blind BTDS 10 or 20 Buprenorphine transdermal patches (BTDS) 10 or 20 mcg/h applied for 7-day wear	Double-blind Placebo Placebo patches to match the BTDS patches applied for 7-day wear
Overall Study Withdrawal by Subject	7	13
Overall Study Adverse Event	44	30
Overall Study Lost to Follow-up	4	3
Overall Study Lack of Efficacy	14	39
Overall Study Administrative	4	9

Baseline Characteristics

Buprenorphine Transdermal System (BTDS) in Subjects w/Mod-sev Osteoarthritis (OA) Chronic Pain of Knee

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-blind BTDS 10 or 20 n=282 Participants Buprenorphine transdermal patches (BTDS) 10 or 20 mcg/h applied for 7-day wear	Double-blind Placebo n=285 Participants Placebo patches to match the BTDS patches applied for 7-day wear	Total n=567 Participants Total of all reporting groups
Age Continuous	59.1 years STANDARD_DEVIATION 9.75 • n=5 Participants	59.1 years STANDARD_DEVIATION 9.77 • n=7 Participants	59.1 years STANDARD_DEVIATION 9.75 • n=5 Participants
Sex: Female, Male Female	175 Participants n=5 Participants	181 Participants n=7 Participants	356 Participants n=5 Participants
Sex: Female, Male Male	107 Participants n=5 Participants	104 Participants n=7 Participants	211 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 hours (week 12)

Population: The full analysis population is the group of subjects who were randomized and received at least 1 dose of double-blind study drug

"Average pain over the last 24 hours" scores of the study knee at week 12 was evaluated on an 11-point scale: 0 = no pain, 10 = worst pain imaginable, recorded daily.

Outcome measures

Outcome measures
Measure	Double-blind BTDS 10 or 20 n=283 Participants Buprenorphine transdermal patches (BTDS) 10 or 20 mcg/h applied for 7-day wear	Double-blind Placebo n=287 Participants Placebo patches to match the BTDS patches applied for 7-day wear
"Average Pain Over the Last 24 Hours" Score of the Study Knee at Week 12 of the Double Blind Phase. Double-blind Week 12 (Visit 8)	3.82 units on a scale Standard Deviation 2.644	4.22 units on a scale Standard Deviation 2.644
"Average Pain Over the Last 24 Hours" Score of the Study Knee at Week 12 of the Double Blind Phase. Screening (Visit 2)	7.16 units on a scale Standard Deviation 1.340	7.06 units on a scale Standard Deviation 1.300
"Average Pain Over the Last 24 Hours" Score of the Study Knee at Week 12 of the Double Blind Phase. Prerandomization (Visit 3)	2.63 units on a scale Standard Deviation 1.292	2.74 units on a scale Standard Deviation 1.186

SECONDARY outcome

Timeframe: 10 weeks

Population: Subjects in the full analysis population who took at least 1 dose of supplemental analgesic medication.

Subjects were permitted to take sponsor-provided supplemental analgesic medication after week 1 of the double-blind treatment (acetaminophen or ibuprofen).

Outcome measures

Outcome measures
Measure	Double-blind BTDS 10 or 20 n=136 Participants Buprenorphine transdermal patches (BTDS) 10 or 20 mcg/h applied for 7-day wear	Double-blind Placebo n=154 Participants Placebo patches to match the BTDS patches applied for 7-day wear
Mean Daily Number of Tablets of Nonopioid Supplemental Analgesic Used From Week 2 to 12 of the Double-blind Phase.	0.701 tablets Standard Deviation 0.8139	0.740 tablets Standard Deviation 0.8566

SECONDARY outcome

Timeframe: Weeks 4, 8, and 12 of the double-bind phase

Population: Full Analysis Population (N = 570) consisted of subjects who were randomized and received at least 1 dose of double-blind study drug.

The MOS Sleep Scale consists of 12 individual items (4 sleep disturbance, 2 sleep adequacy, 1 quantity of sleep and optimal sleep, 3 somnolence, 1 snoring, and 1 shortness of breath) and takes 5 to 10 minutes to complete. Question 1 is scored on a scale of 1 to 5 ( 1 = 0-15 min to more than 60 min) and Questions 2 to 12 are scored on a scale of 1 to 6 (1 = all of the time to 6 = none of the time. The Sleep Disturbance Subscale score is derived from the scores to Questions 1, 3, 7, and 8 and ranges from 0 to 100, where higher scores indicate greater sleep disturbance.

Outcome measures

Outcome measures
Measure	Double-blind BTDS 10 or 20 n=283 Participants Buprenorphine transdermal patches (BTDS) 10 or 20 mcg/h applied for 7-day wear	Double-blind Placebo n=287 Participants Placebo patches to match the BTDS patches applied for 7-day wear
Sleep Disturbance Subscale of the MOS-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase. Prerandomization	23.23 units on a scale Standard Deviation 19.583	26.04 units on a scale Standard Deviation 20.822
Sleep Disturbance Subscale of the MOS-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase. Screening	49.51 units on a scale Standard Deviation 24.790	51.23 units on a scale Standard Deviation 25.945
Sleep Disturbance Subscale of the MOS-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase. Week 4	27.22 units on a scale Standard Deviation 23.086	35.08 units on a scale Standard Deviation 25.565
Sleep Disturbance Subscale of the MOS-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase. Week 8	27.46 units on a scale Standard Deviation 23.795	34.78 units on a scale Standard Deviation 24.715
Sleep Disturbance Subscale of the MOS-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase. Week 12	29.60 units on a scale Standard Deviation 25.177	33.63 units on a scale Standard Deviation 25.606

Adverse Events

Double-blind BTDS

Serious events: 13 serious events

Other events: 108 other events

Deaths: 0 deaths

Double-blind Placebo

Serious events: 3 serious events

Other events: 53 other events

Deaths: 0 deaths

Open-label Run-in Period

Serious events: 5 serious events

Other events: 520 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Double-blind BTDS n=282 participants at risk Buprenorphine transdermal patches (BTDS) 10 or 20 mcg/h applied for 7-day wear	Double-blind Placebo n=285 participants at risk Placebo patches to match the BTDS patches applied for 7-day wear	Open-label Run-in Period n=1151 participants at risk The open-label run-in period was designed with duration of time sufficient to select those subjects who both tolerated and responded to treatment with BTDS 10 or BTDS 20 (an enriched design). During this period, subjects were required to discontinue use of all nonstudy drugs used for the treatment of chronic pain and no supplemental analgesic medications were allowed. Subjects who did not tolerate BTDS 5 were discontinued from the study.
Gastrointestinal disorders Nausea	12.1% 34/282 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	4.9% 14/285 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	21.0% 242/1151 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.
Gastrointestinal disorders Vomiting	6.7% 19/282 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	1.8% 5/285 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	7.8% 90/1151 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.
Gastrointestinal disorders Constipation	6.7% 19/282 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	0.70% 2/285 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	7.8% 90/1151 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.
General disorders Application site pruritus	11.0% 31/282 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	6.3% 18/285 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	8.3% 96/1151 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.
General disorders Application site erythema	7.4% 21/282 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	4.9% 14/285 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	3.2% 37/1151 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.
General disorders Application site rash	5.7% 16/282 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	3.5% 10/285 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	3.2% 37/1151 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.
General disorders Fatigue	2.5% 7/282 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	1.1% 3/285 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	5.4% 62/1151 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.
Nervous system disorders Dizziness	2.5% 7/282 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	2.1% 6/285 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	11.5% 132/1151 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.
Nervous system disorders Somnolence	3.5% 10/282 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	1.8% 5/285 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	10.3% 119/1151 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.
Nervous system disorders Headache	6.4% 18/282 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	7.0% 20/285 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	8.1% 93/1151 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.
Psychiatric disorders Anxiety	5.7% 16/282 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	0.70% 2/285 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.	1.0% 12/1151 • Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days. AEs were obtained through spontaneous reports and subject interview.

Additional Information

Clinical Leader, Executive Medical Director

Purdue Pharma

Phone: 800-733-1333

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60