Clinical trial NCT01637922: Drug Interaction Study With BI 201335 and Methadone or Buprenorphine/Naloxone
Official title: Effect of Multiple Dosing With BI 201335 on the Safety, Pharmacokinetics and Pharmacodynamics of Steady-state Methadone and Buprenorphine/Naloxone in Subjects on Stable Addiction Management Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2012-07-11
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Otherwise healthy subjects who are currently bein maintained on either methadone or buprenorphine/naloxone for opioid maintenance therapy who have been on a stable dose for at least 30 days will be administered BI 201335 daily to determine if a drug interaction occurs between BI 201335 and either methadone or buprenorphine/naloxone.


Eligibility criteria: Inclusion criteria:

1. stable dose of either methadone or buprenorphine/naloxone for 30 days for opioid maintenance therapy.
2. Male and female volunteers with a body mass index (BMI) = 18.5 and \< 32 with a minimum weight of 50kg.

Exclusion criteria:

1. any other significant medical illness of clinical significance.
2. history of rash or photosensitivity
3. chronic or acute infections including HIV, hepatitis B and hepatitis C.
4. history of allergy considered significant for this study
5. intake of any other medications except for methadone or buprenorphine/naloxone.
6. QTc on electrocardiogram (ECG) \> 470.
7. use of any other investigational drug within 30 days of the study.
8. drug or alcohol abuse (other than the defined opioid maintenance therapy with either methadone or buprenorphine/naloxone)
9. blood donation of more than 100mL within four weeks of the trial.
10. excessive physical activities one week prior to and during the trial.
11. any clinically relevant laboratory value.
12. concomitant use of any food product known to alter P450 or P-gp activity such as grapefruit juice, seville oranges and St. John's Wort.
13. inadequate venous access

    For women of childbearing potential:
14. pregnancy or planning to become pregnant within 3 months of the trial
15. positive pregnancy test at screening visit
16. no proof of sterilization or unwilling or unable to use a double barrier method of birth control during the study and up to 3 months after the study.
17. lactation with active breastfeeding from screening up to 30 days after last study visit.

Primary outcomes:
measure: R-methadone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9.
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: R-methadone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9.
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: R-methadone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9.
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: S-methadone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: S-methadone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: S-methadone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: Buprenorphine: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9.
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: Buprenorphine: Geometric Mean Steady-state Cmax on Day 1 and on Day 9.
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: Buprenorphine: Geometric Mean Steady-state C24hr on Day 1 and on Day 9.
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: Norbuprenorphine: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9.
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: Norbuprenorphine: Geometric Mean Steady-state Cmax on Day 1 and on Day 9.
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: Norbuprenorphine: Geometric Mean Steady-state C24hr on Day 1 and on Day 9.
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: Naloxone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9.
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: Naloxone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9.
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
measure: Naloxone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9.
timeFrame: 0 hours, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours on Day 1 and Day 9
Secondary outcomes:
measure: Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline
timeFrame: Baseline, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12 and End of treatment
measure: Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline
timeFrame: Baseline, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12 and End of treatment
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: 1220.57.0001 Boehringer Ingelheim Investigational Site
state: Georgia
city: Overland Park
country: United States
facility: 1220.57.0002 Boehringer Ingelheim Investigational Site
state: Kansas
city: Salt Lake City
country: United States
facility: 1220.57.0003 Boehringer Ingelheim Investigational Site
state: Utah
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Joseph D, Schobelock MJ, Riesenberg RR, Vince BD, Webster LR, Adeniji A, Elgadi M, Huang F. Effect of steady-state faldaprevir on the pharmacokinetics of steady-state methadone and buprenorphine-naloxone in subjects receiving stable addiction management therapy. Antimicrob Agents Chemother. 2015 Jan;59(1):498-504. doi: 10.1128/AAC.04046-14. Epub 2014 Nov 10.