Hepatitis C
Conditions
Keywords
Hepatitis C, HCV, Hepatitis C Virus, HCV negative, Protease inhibitor, Methadone, TMC435
Brief summary
The purpose of this study is to evaluate the effect of steady-state (constant concentration of medication in the blood) TMC435 (150 mg, once a day) on the steady state pharmacokinetics (what the body does to the medication) of R- and S-methadone.
Detailed description
This is an open label (all people know the identity of the intervention) drug-drug interaction (TMC435 versus methadone) study. Approximately 12 hepatitis C virus-negative opioid-dependent participants on stable maintenance therapy (for at least 30 days before screening) will be enrolled in the study. The study will consist of 3 phases: 1) Run-in phase: during this phase, participants will take individualized (dose of methadone will be adjusted for each participant between a range of 30 and 150 mg daily) dose of methadone from Day -14 (14 days before the first intake of TMC435) till Day -1 (1 day before the first intake of TMC435), which will be supervised by the medical staff. 2) 7 days treatment phase: during this phase, the participants will take 150 mg dose of TMC435 once daily from Day 1 to Day 7 orally (by mouth) plus the individualized dose of methadone which will be supervised by the medical staff. 3) Follow-up phase: during this phase, the participants will continue to take only the individualized dose of methadone for 30-32 days. Safety evaluations will include assessment of adverse events, clinical laboratory tests, cardiovascular safety, physical examination and alcohol breath test. The total study duration will be of 22 days excluding screening and follow-up phase.
Interventions
DRUGTMC435
Participants will receive 150 mg dose of TMC435 orally (by mouth) once daily for 7 days of treatment (from Day 1 to Day 7).
OTHERMethadone
Participants will receive supervised individualized methadone dose (dose of methadone will be adjusted for each participant between a range of 30 and 150 mg daily \[extremes included\]) from Day -14 untill Day 8. Participants will continue to receive individualized methadone during follow up of 30 to 32 days.
Sponsors
Tibotec Pharmaceuticals, Ireland
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Receiving once daily oral methadone maintenance therapy at a stable individualized dose of 30 to 130 mg once daily for at least 30 days prior to screening * Agreeing not to change the current methadone dose from screening until Day7 included and to have a daily observed and documented methadone intake from Day-14 until Day8 and to have a daily observed and documented TMC435 intake from Day1 until Day 7 * Having obtained approval from his/her addiction physician for participation in the trial and addiction physician agrees to provide medical care for the volunteer after discharge from the testing facility
Exclusion criteria
* No female of childbearing potential, except if using effective birth control methods during the trial and for at least 30 days after the end of the treatment period * No positive testing for drugs of abuse * No positive testing for Hepatitis A, B and C and for HIV1 and 2 * Impaired liver disease or other clinically relevant diseases
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Fluctuation index of TMC435, ie, percentage fluctuation (variation between maximum and minimum concentration at steady-state) | On Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose and on Day 8 at 24 hour postdose |
| Minimum plasma concentration between 0 hour and dosing interval of TMC435 | On Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose and on Day 8 at 24 hour postdose |
| Average steady-state plasma concentration of TMC435 | On Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose and on Day 8 at 24 hour postdose |
| Time to reach the maximum plasma concentration of TMC435 | On Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose and on Day 8 at 24 hour postdose |
| Area under the curve from time of administration up to 24 hours post dosing of TMC435 | On Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose and on Day 8 at 24 hour postdose |
| Predose plasma concentration of S-methadone | Day -4 to Day 6 |
| Maximum plasma concentration of S-methadone | On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose |
| Minimum plasma concentration between 0 hour and dosing interval of S-methadone | On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose |
| Average steady-state plasma concentration of S-methadone | On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose |
| Time to reach the maximum plasma concentration of S-methadone | On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose |
| Area under the curve from time of administration up to 24 hours post dosing of S-methadone | On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose |
| Fluctuation index of S-methadone, ie, percentage fluctuation (variation between maximum and minimum concentration at steady-state) | On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose |
| Predose plasma concentration of R-methadone | Day -4 to Day 7 |
| Maximum plasma concentration of R-methadone | On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose |
| Minimum plasma concentration between 0 hour and dosing interval of R- and S-methadone | On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose |
| Average steady-state plasma concentration of R-methadone | On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose |
| Time to reach the maximum plasma concentration of R-methadone | On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose |
| Area under the curve from time of administration up to 24 hours post dosing of R-methadone | On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose |
| Fluctuation index of R-methadone, ie, percentage fluctuation (variation between maximum and minimum concentration at steady-state) | On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose |
| Predose plasma concentration of TMC435 | Day 4 to Day 6 |
| Maximum plasma concentration of TMC435 | On Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose and on Day 8 at 24 hour postdose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Desires for Drugs Questionnaire | On Day-1 and Day 7 at 2 hour and 4 hour predose; on Day-7, Day-2, and Day 1 to Day 6 at predose | — |
| Resting pupil diameter | On Day-1 and Day 7 at 2 hour and 4 hour predose; on Day-7, Day-2, and Day 1 to Day 6 at predose | Pupillometry will be performed and resting pupil diameter will be assessed with a validated pupillograph. |
| Number of participants with adverse events as a measure of safety and tolerability | Up to 30 to 32 days after the last medication dose | — |
| Short Opiate Withdrawal Scale Scores | On Day-1 and Day 7 at 2 hour and 4 hour predose; on Day-7, Day-2, and Day 1 to Day 6 at predose | Short Opiate Withdrawal Scale is used for the assessment of opioid withdrawal. It consists of 10 items and items are designed to measure symptoms, on a scale from 0 to 3 (0= None, 1= Mild, 2= Moderate, 3= Severe). The total score ranges from 0 (best) to 30 (worst). Higher scores indicate worsening. |
Countries
Canada
Outcome results
None listed