Trial Outcomes & Findings for Buprenorphine Accumulation and Description of Its Metabolites During Co-Medication of Buprenorphine Transdermal System (BTDS) and Ketoconazole (NCT NCT01259115)
NCT ID: NCT01259115
Last Updated: 2014-05-19
Results Overview
AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration) of buprenorphine transdermal patch 10 with and without ketoconazole 200 mg oral twice daily. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or Ketoconazole placebo (orally twice daily) between days 17 and 27.
COMPLETED
PHASE1
20 participants
BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25
2014-05-19
Participant Flow
21-Oct-2002 (first subject, first visit) to 20-Jun-2003 (last subject, last visit). Study conducted at 1 site in New Orleans, LA.
Healthy male and female subjects aged 18 to 54 years, demonstrating successful inhibition of CYP3A4 using the EBT (erythromycin breath test) probe were randomized.
Participant milestones
| Measure |
Sequence A: BTDS 10 With Ketoconazole (Test) First
Period 1: Buprenorphine transdermal system (BTDS) 10 with ketoconazole 200 mg tablets twice daily (Test) first;
Washout Period of 4 to 18 days;
Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
Sequence B: BTDS 10 With Placebo (Reference) First
Period 1: Buprenorphine transdermal system (BTDS) 10 with ketoconazole placebo tablets twice daily (Reference) first
Washout Period of 4 to 18 days;
Period 2: BTDS 10 with ketoconazole 200 mg tablets twice daily.
|
|---|---|---|
|
Period 1
STARTED
|
10
|
10
|
|
Period 1
COMPLETED
|
7
|
9
|
|
Period 1
NOT COMPLETED
|
3
|
1
|
|
Period: Washout Period of 4 to 18 Days
STARTED
|
7
|
9
|
|
Period: Washout Period of 4 to 18 Days
COMPLETED
|
7
|
9
|
|
Period: Washout Period of 4 to 18 Days
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
7
|
9
|
|
Period 2
COMPLETED
|
6
|
9
|
|
Period 2
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Sequence A: BTDS 10 With Ketoconazole (Test) First
Period 1: Buprenorphine transdermal system (BTDS) 10 with ketoconazole 200 mg tablets twice daily (Test) first;
Washout Period of 4 to 18 days;
Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
Sequence B: BTDS 10 With Placebo (Reference) First
Period 1: Buprenorphine transdermal system (BTDS) 10 with ketoconazole placebo tablets twice daily (Reference) first
Washout Period of 4 to 18 days;
Period 2: BTDS 10 with ketoconazole 200 mg tablets twice daily.
|
|---|---|---|
|
Period 1
Adverse Event
|
1
|
0
|
|
Period 1
Protocol Violation
|
2
|
0
|
|
Period 1
Lost to Follow-up
|
0
|
1
|
|
Period 2
Adverse Event
|
1
|
0
|
Baseline Characteristics
Buprenorphine Accumulation and Description of Its Metabolites During Co-Medication of Buprenorphine Transdermal System (BTDS) and Ketoconazole
Baseline characteristics by cohort
| Measure |
Overall Study
n=20 Participants
Subjects received BTDS 10 with ketoconazole 200 mg or ketoconazole placebo tablets twice daily in period 1; Washout Period for 4 to 18 days; Subjects received BTDS 10 with ketoconazole 200 mg or ketoconazole placebo tablets twice daily in period 2.
|
|---|---|
|
Age, Continuous
|
31.8 years
STANDARD_DEVIATION 8.62 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25Population: The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid pharmacokinetic metric.
AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration) of buprenorphine transdermal patch 10 with and without ketoconazole 200 mg oral twice daily. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or Ketoconazole placebo (orally twice daily) between days 17 and 27.
Outcome measures
| Measure |
BTDS 10 With Ketoconazole
n=18 Participants
Period 1: BTDS 10 with ketoconazole 200 mg tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
BTDS 10 With Ketoconazole Placebo
n=16 Participants
Period 1: BTDS 10 with ketoconazole placebo tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole 200 mg twice daily.
|
|---|---|---|
|
AUCt of Buprenorphine With and Without Ketoconazole.
|
16354.8 pg/mL*h
Standard Deviation 6197.3
|
16627.9 pg/mL*h
Standard Deviation 5559.7
|
PRIMARY outcome
Timeframe: BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25Population: The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid pharmacokinetic metric.
AUCinf (the area under the plasma-concentration time course profile from time 0 \[dosing\] to infinity) of buprenorphine transdermal patch 10 with and without ketoconazole 200 mg oral twice daily. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27.
Outcome measures
| Measure |
BTDS 10 With Ketoconazole
n=13 Participants
Period 1: BTDS 10 with ketoconazole 200 mg tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
BTDS 10 With Ketoconazole Placebo
n=9 Participants
Period 1: BTDS 10 with ketoconazole placebo tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole 200 mg twice daily.
|
|---|---|---|
|
AUCinf of Buprenorphine With and Without Ketoconazole.
|
18238.5 pg /mL•h
Standard Deviation 6624.5
|
19012.5 pg /mL•h
Standard Deviation 6599.2
|
PRIMARY outcome
Timeframe: BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25Population: The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric.
Cmax (maximum observed plasma concentration) of buprenorphine transdermal patch 10 with and without ketoconazole 200 mg oral tablets twice daily, Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27.
Outcome measures
| Measure |
BTDS 10 With Ketoconazole
n=18 Participants
Period 1: BTDS 10 with ketoconazole 200 mg tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
BTDS 10 With Ketoconazole Placebo
n=16 Participants
Period 1: BTDS 10 with ketoconazole placebo tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole 200 mg twice daily.
|
|---|---|---|
|
Cmax of Buprenorphine With and Without Ketoconazole.
|
142.2 pg/mL
Standard Deviation 53.7
|
145.5 pg/mL
Standard Deviation 48.7
|
PRIMARY outcome
Timeframe: BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25Population: The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric.
For nor-buprenorphine pharmacokinetic metric, AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration). Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27.
Outcome measures
| Measure |
BTDS 10 With Ketoconazole
n=16 Participants
Period 1: BTDS 10 with ketoconazole 200 mg tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
BTDS 10 With Ketoconazole Placebo
n=11 Participants
Period 1: BTDS 10 with ketoconazole placebo tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole 200 mg twice daily.
|
|---|---|---|
|
AUCt of Nor-buprenorphine With and Without Ketoconazole
|
5091.0 pg/mL*h
Standard Deviation 3208.3
|
3207.8 pg/mL*h
Standard Deviation 1746.4
|
PRIMARY outcome
Timeframe: BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25Population: The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric.
For nor-buprenorphine pharmacokinetic metric, AUCinf (the area under the plasma-concentration time course profile from time 0 \[dosing\] to infinity). Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27.
Outcome measures
| Measure |
BTDS 10 With Ketoconazole
n=1 Participants
Period 1: BTDS 10 with ketoconazole 200 mg tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
BTDS 10 With Ketoconazole Placebo
Period 1: BTDS 10 with ketoconazole placebo tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole 200 mg twice daily.
|
|---|---|---|
|
AUCinf of Nor-buprenorphine With and Without Ketoconazole
|
6767.9 pg/mL*h
Standard Deviation 0
|
—
|
PRIMARY outcome
Timeframe: BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25Population: The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric.
For nor-buprenorphine pharmacokinetic metric, Cmax (maximum observed plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27.
Outcome measures
| Measure |
BTDS 10 With Ketoconazole
n=16 Participants
Period 1: BTDS 10 with ketoconazole 200 mg tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
BTDS 10 With Ketoconazole Placebo
n=11 Participants
Period 1: BTDS 10 with ketoconazole placebo tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole 200 mg twice daily.
|
|---|---|---|
|
Cmax of Nor-buprenorphine With and Without Ketoconazole
|
63.4 pg/mL
Standard Deviation 25.9
|
44.6 pg/mL
Standard Deviation 11.1
|
PRIMARY outcome
Timeframe: BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25Population: The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric.
For nor-buprenorphine glucuronide pharmacokinetic metrics, AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27.
Outcome measures
| Measure |
BTDS 10 With Ketoconazole
n=18 Participants
Period 1: BTDS 10 with ketoconazole 200 mg tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
BTDS 10 With Ketoconazole Placebo
n=16 Participants
Period 1: BTDS 10 with ketoconazole placebo tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole 200 mg twice daily.
|
|---|---|---|
|
AUCt of Nor-buprenorphine Glucuronide With and Without Ketoconazole
|
21376.9 pg/mL*h
Standard Deviation 9808.2
|
15840.5 pg/mL*h
Standard Deviation 5034.5
|
PRIMARY outcome
Timeframe: BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25Population: The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric.
For nor-buprenorphine glucuronide pharmacokinetic metrics, AUCinf (the area under the plasma-concentration time course profile from time 0 \[dosing\] to infinity) log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27.
Outcome measures
| Measure |
BTDS 10 With Ketoconazole
Period 1: BTDS 10 with ketoconazole 200 mg tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
BTDS 10 With Ketoconazole Placebo
n=3 Participants
Period 1: BTDS 10 with ketoconazole placebo tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole 200 mg twice daily.
|
|---|---|---|
|
AUCinf of Nor-buprenorphine Glucuronide With and Without Ketoconazole
|
—
|
17318.9 pg/mL*h
Standard Deviation 657.2
|
PRIMARY outcome
Timeframe: BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25Population: The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric.
For nor-buprenorphine glucuronide pharmacokinetic metric, Cmax (maximum observed plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27.
Outcome measures
| Measure |
BTDS 10 With Ketoconazole
n=18 Participants
Period 1: BTDS 10 with ketoconazole 200 mg tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
BTDS 10 With Ketoconazole Placebo
n=16 Participants
Period 1: BTDS 10 with ketoconazole placebo tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole 200 mg twice daily.
|
|---|---|---|
|
Cmax of Nor-buprenorphine Glucuronide With and Without Ketoconazole
|
218.2 pg/mL
Standard Deviation 99.4
|
141.9 pg/mL
Standard Deviation 47.6
|
PRIMARY outcome
Timeframe: BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25Population: The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric.
For buprenorphine-3-glucuronide pharmacokinetic metric, AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27.
Outcome measures
| Measure |
BTDS 10 With Ketoconazole
n=5 Participants
Period 1: BTDS 10 with ketoconazole 200 mg tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
BTDS 10 With Ketoconazole Placebo
Period 1: BTDS 10 with ketoconazole placebo tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole 200 mg twice daily.
|
|---|---|---|
|
AUCt of Buprenorphine-3-glucuronide With and Without Ketoconazole
|
342.4 pg/mL*h
Standard Deviation 488.2
|
—
|
PRIMARY outcome
Timeframe: BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25Population: The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric.
For buprenorphine-3-glucuronide pharmacokinetic metric, AUCinf (the area under the plasma-concentration time course profile from time 0 \[dosing\] to infinity), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25Population: The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric.
For buprenorphine-3-glucuronide pharmacokinetic metric, Cmax (maximum observed plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27.
Outcome measures
| Measure |
BTDS 10 With Ketoconazole
n=5 Participants
Period 1: BTDS 10 with ketoconazole 200 mg tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
BTDS 10 With Ketoconazole Placebo
Period 1: BTDS 10 with ketoconazole placebo tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole 200 mg twice daily.
|
|---|---|---|
|
Cmax of Buprenorphine-3-glucuronide With and Without Ketoconazole
|
88.5 pg/mL
Standard Deviation 85.6
|
—
|
SECONDARY outcome
Timeframe: One time at screening and one time during ketoconazole treatmentPopulation: Enrolled Population: All subjects who participated in the study. CYP3A4 Inhibition was only done when subjects were on Ketoconazole.
As part of subject screening, Erythromycin Breath Tests (EBT) were done on all potential subjects (enrolled population). CYP 3A4 inhibition was calculated by taking the difference of the baseline 14C erythromycin metabolism, subtracting the 14C erythromycin metabolism during ketoconazole treatment, dividing this difference by the baseline 14C erythromycin metabolism, and multiplying by 100 to express results in the form of percent inhibition. CYP3A4 inhibition was only done when subjects were on ketoconazole.
Outcome measures
| Measure |
BTDS 10 With Ketoconazole
n=20 Participants
Period 1: BTDS 10 with ketoconazole 200 mg tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
BTDS 10 With Ketoconazole Placebo
Period 1: BTDS 10 with ketoconazole placebo tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole 200 mg twice daily.
|
|---|---|---|
|
CYP3A4 Inhibition by Observation of Plasma Nor-buprenorphine Production Assessed by the Erythromycin Breath Test.
All subjects [N = 20]
|
64.49 Percentage of participants
Standard Deviation 15.69
|
—
|
|
CYP3A4 Inhibition by Observation of Plasma Nor-buprenorphine Production Assessed by the Erythromycin Breath Test.
Inhibition ≤ 50% [n = 4]
|
37.50 Percentage of participants
Standard Deviation 4.11
|
—
|
|
CYP3A4 Inhibition by Observation of Plasma Nor-buprenorphine Production Assessed by the Erythromycin Breath Test.
Inhibition >50% but ≤ 70% [n = 8]
|
64.50 Percentage of participants
Standard Deviation 4.61
|
—
|
|
CYP3A4 Inhibition by Observation of Plasma Nor-buprenorphine Production Assessed by the Erythromycin Breath Test.
Inhibition > 70% [n = 8]
|
77.98 Percentage of participants
Standard Deviation 3.94
|
—
|
SECONDARY outcome
Timeframe: The first day of study drug administration to 30 days after the last dose of study drug.Population: Safety Population: Safety analyses were performed on all subjects who received at least 1 dose of study drug and for whom at least 1 postdose safety observation was recorded.
Safety assessments consisted of monitoring and recording medical history, physical examinations, vital signs (including temperature, heart rate, blood pressure and respiratory rate), reports of adverse experiences, and laboratory abnormalities (including electrocardiogram \[ECG\]).
Outcome measures
| Measure |
BTDS 10 With Ketoconazole
n=19 Participants
Period 1: BTDS 10 with ketoconazole 200 mg tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily.
|
BTDS 10 With Ketoconazole Placebo
n=17 Participants
Period 1: BTDS 10 with ketoconazole placebo tablets twice daily; Washout: Day 12 to 15; Period 2: BTDS 10 with ketoconazole 200 mg twice daily.
|
|---|---|---|
|
The Number of Participants With Adverse Events (AEs) as a Measure of Safety.
Deaths
|
0 participants
|
0 participants
|
|
The Number of Participants With Adverse Events (AEs) as a Measure of Safety.
Serious Adverse Events
|
0 participants
|
0 participants
|
|
The Number of Participants With Adverse Events (AEs) as a Measure of Safety.
Adverse Events in 4% or more of subjects
|
19 participants
|
16 participants
|
Adverse Events
BTDS With Ketoconazole
BTDS With Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
BTDS With Ketoconazole
n=19 participants at risk
Subjects who were treated with buprenorphine transdermal patch 10 mcg/hour with ketoconazole 200 mg oral tablets twice daily.
|
BTDS With Placebo
n=17 participants at risk
Subjects who were treated with buprenorphine transdermal patch 10 mcg/hour with ketoconazole placebo oral tablets twice daily.
|
|---|---|---|
|
Gastrointestinal disorders
Cardiospasm
|
0.00%
0/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
5.9%
1/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
5.9%
1/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Gastrointestinal disorders
Dyspepsia
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
11.8%
2/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Gastrointestinal disorders
Dysphagia
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
0.00%
0/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Gastrointestinal disorders
Nausea
|
26.3%
5/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
23.5%
4/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
5.9%
1/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Gastrointestinal disorders
Tooth disorder
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
0.00%
0/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Gastrointestinal disorders
Vomiting
|
21.1%
4/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
11.8%
2/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
General disorders
Abdominal pain
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
5.9%
1/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
General disorders
Back pain
|
0.00%
0/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
5.9%
1/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
General disorders
Pain
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
0.00%
0/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
General disorders
Headache
|
26.3%
5/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
17.6%
3/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Blood and lymphatic system disorders
Ecchymosis
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
0.00%
0/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
0.00%
0/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Metabolism and nutrition disorders
Dehydration
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
0.00%
0/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Metabolism and nutrition disorders
Creatinine increased
|
10.5%
2/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
0.00%
0/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Infections and infestations
Infection
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
0.00%
0/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Injury, poisoning and procedural complications
Accidental Injury
|
0.00%
0/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
5.9%
1/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
0.00%
0/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
5.9%
1/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Nervous system disorders
Dizziness
|
31.6%
6/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
29.4%
5/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Nervous system disorders
Somnolence
|
0.00%
0/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
11.8%
2/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
0.00%
0/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
0.00%
0/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Skin and subcutaneous tissue disorders
Acne
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
11.8%
2/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Skin and subcutaneous tissue disorders
Erythema at site
|
68.4%
13/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
64.7%
11/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
15.8%
3/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
5.9%
1/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Skin and subcutaneous tissue disorders
Pruritus at site
|
36.8%
7/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
29.4%
5/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
0.00%
0/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Eye disorders
Dry eyes
|
0.00%
0/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
5.9%
1/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Eye disorders
Photophobia
|
0.00%
0/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
5.9%
1/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Renal and urinary disorders
Urination impaired
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
5.9%
1/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Renal and urinary disorders
Leukorrhea
|
5.3%
1/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
0.00%
0/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
|
Vascular disorders
Vasodilatation
|
15.8%
3/19 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
11.8%
2/17 • All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
|
Additional Information
Executive Medical Director, Clinical Pharmacology
Purdue Pharma L.P.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60