Hepatitis C
Conditions
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.
Interventions
DRUGBI 201335
BI 201335 for 9 days
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Naloxone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9. | 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 | These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose |
| Naloxone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9. | 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 | These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours. |
| Naloxone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9. | 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 | These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state. |
| R-methadone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9. | 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 | These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours. |
| R-methadone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9. | 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 | These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state. |
| R-methadone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9. | 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 | These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose |
| S-methadone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9 | 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 | These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours. |
| S-methadone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9 | 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 | These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state. |
| S-methadone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9 | 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 | These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose |
| Buprenorphine: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9. | 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 | These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours. |
| Buprenorphine: Geometric Mean Steady-state Cmax on Day 1 and on Day 9. | 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 | These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state. |
| Buprenorphine: Geometric Mean Steady-state C24hr on Day 1 and on Day 9. | 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 | These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose |
| Norbuprenorphine: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9. | 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 | These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours. |
| Norbuprenorphine: Geometric Mean Steady-state Cmax on Day 1 and on Day 9. | 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 | These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state. |
| Norbuprenorphine: Geometric Mean Steady-state C24hr on Day 1 and on Day 9. | 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 | These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | 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 | The SOWS is a subjective scale self-evaluated by the subject. The SOWS shows items reflecting the common motor, autonomic, gastrointestinal, musculo-skeletal, and psychic symptoms of opiate withdrawal. Subjects are instructed to rate each symptom on a scale of 0 to 4 (0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely) at designated times \[c.f. Section 3.1\]. The minimum possible SOWS score is 0, the maximum 64. The following subjective criteria are answered by the subject using the scale below: 1) I feel anxious, 2) I feel like yawning 3) I am perspiring, 4) My eyes are watering, 5) My nose is running, 6) I have goose flesh, 7) I am shaking 8) I have hot flushes, 9) I have cold flushes, 10) My bones and muscles ache, 11) I feel restless, 12) I feel nauseous, 13) I feel like vomiting, 14) My muscles twitch, 15) I have cramps in my stomach, 16) I feel like shooting up now. Higher score indicates increasing severity of opiate withdrawal syndrome. |
| Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | 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 | The OOWS is conducted by a trained independent examiner for either the presence or absence of the following symptoms during a 10 minute observation period at designated times during the trial. The minimum possible OOWS score is 0 and the maximum possible score is 13. Objective criteria: Yawning, Rhinorrhoea, Piloerection, perspiration, lacrimation, mydriasis, hot and cold flushes, restlessness, vomiting, tremors, anxiety, muscle twitches, abdominal cramps. Higher score indicates increasing severity of opiate withdrawal syndrome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Methadone Group patients on stable methadone therapy (at least 30 days) up to a maximum of 180mg per day. Days 1-13.
BI 201335(faldaprevir): BI 201335(faldaprevir) for days 3 to 9. | 15 |
| Buprenorphine/Naloxone (Suboxone) patients on stable buprenorphine/naloxone therapy (at least 30 days) up to a maximum dose of 24mg/6mg per day. Days 1-13.
BI 201335(faldaprevir): BI 201335(faldaprevir) for days 3 to 9. | 19 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Methadone Group | Buprenorphine/Naloxone (Suboxone) | Total |
|---|---|---|---|
| Age, Continuous | 35.4 years STANDARD_DEVIATION 11 | 34.1 years STANDARD_DEVIATION 8.7 | 34.6 years STANDARD_DEVIATION 9.7 |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 11 Participants | 16 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 15 | 18 / 19 |
| serious Total, serious adverse events | 0 / 15 | 0 / 19 |
Outcome results
Primary
Buprenorphine: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9.
These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours.
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | Buprenorphine: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9. | BUPRENORPHINE with FDV (Day 9) | 58700 [pg*h/ml] | Geometric Coefficient of Variation 73.1 |
| Methadone Group | Buprenorphine: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9. | BUPRENORPHINE alone (Day 1) | 54000 [pg*h/ml] | Geometric Coefficient of Variation 86.5 |
Comparison: BUPRENORPHINE(BUP) + Faldaprevir(FDV) on Day 9 vs. BUPRENORPHINE(BUP) alone on Day 1p-value: 0.164290% CI: [85.14, 138.8]ANOVA
Primary
Buprenorphine: Geometric Mean Steady-state C24hr on Day 1 and on Day 9.
These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | Buprenorphine: Geometric Mean Steady-state C24hr on Day 1 and on Day 9. | BUPRENORPHINE with FDV (Day 9) | 1110 [pg/mL] | Geometric Coefficient of Variation 99 |
| Methadone Group | Buprenorphine: Geometric Mean Steady-state C24hr on Day 1 and on Day 9. | BUPRENORPHINE alone (Day 1) | 904 [pg/mL] | Geometric Coefficient of Variation 109 |
Comparison: BUPRENORPHINE(BUP) + Faldaprevir(FDV) on Day 9 vs. BUPRENORPHINE(BUP) alone on Day 1p-value: 0.191590% CI: [81.611, 143.883]ANOVA
Primary
Buprenorphine: Geometric Mean Steady-state Cmax on Day 1 and on Day 9.
These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state.
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | Buprenorphine: Geometric Mean Steady-state Cmax on Day 1 and on Day 9. | BUPRENORPHINE with FDV (Day 9) | 7610 [pg/ml] | Geometric Coefficient of Variation 74.5 |
| Methadone Group | Buprenorphine: Geometric Mean Steady-state Cmax on Day 1 and on Day 9. | BUPRENORPHINE alone (Day 1) | 8240 [pg/ml] | Geometric Coefficient of Variation 92 |
Comparison: BUPRENORPHINE(BUP) + Faldaprevir(FDV) on Day 9 vs. BUPRENORPHINE(BUP) alone on Day 1p-value: 0.14290% CI: [73.48, 116.27]ANOVA
Primary
Naloxone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9.
These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours.
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | Naloxone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9. | NALOXONE with FDV (Day 9) | 971 [pg*h/ml] | Geometric Coefficient of Variation 69.8 |
| Methadone Group | Naloxone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9. | NALOXONE alone (Day 1) N=12 | 1000 [pg*h/ml] | Geometric Coefficient of Variation 87.9 |
Comparison: NALOXONE(BUP) + Faldaprevir(FDV) on Day 9 vs. NALOXONE(BUP) alone on Day 1p-value: 0.010790% CI: [85.81, 114.076]ANOVA
Primary
Naloxone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9.
These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Methadone Group | Naloxone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9. | NALOXONE with FDV (Day 9) | 23.4 [pg/mL] |
| Methadone Group | Naloxone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9. | NALOXONE alone (Day 1) | 25.6 [pg/mL] |
Primary
Naloxone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9.
These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state.
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | Naloxone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9. | NALOXONE with FDV (Day 9) | 284 [pg/mL] | Geometric Coefficient of Variation 107 |
| Methadone Group | Naloxone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9. | NALOXONE alone (Day 1) N=13 | 357 [pg/mL] | Geometric Coefficient of Variation 82.9 |
Comparison: NALOXONE(BUP) + Faldaprevir(FDV) on Day 9 vs. NALOXONE(BUP) alone on Day 1p-value: 0.073890% CI: [78.017, 114.054]ANOVA
Primary
Norbuprenorphine: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9.
These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours.
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | Norbuprenorphine: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9. | NORBUPRENORPHINE with FDV (Day 9) | 59200 [pg*h/ml] | Geometric Coefficient of Variation 93.5 |
| Methadone Group | Norbuprenorphine: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9. | NORBUPRENORPHINE alone (Day 1) | 42900 [pg*h/ml] | Geometric Coefficient of Variation 135 |
Comparison: NORBUPRENORPHINE(BUP) + Faldaprevir(FDV) on Day 9 vs. NORBUPRENORPHINE(BUP) alone on Day 1p-value: 0.688990% CI: [97.2, 195.92]ANOVA
Primary
Norbuprenorphine: Geometric Mean Steady-state C24hr on Day 1 and on Day 9.
These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | Norbuprenorphine: Geometric Mean Steady-state C24hr on Day 1 and on Day 9. | NORBUPRENORPHINE with FDV (Day 9) | 2080 [pg/mL] | Geometric Coefficient of Variation 102 |
| Methadone Group | Norbuprenorphine: Geometric Mean Steady-state C24hr on Day 1 and on Day 9. | NORBUPRENORPHINE alone (Day 1) | 2010 [pg/mL] | Geometric Coefficient of Variation 113 |
Comparison: NORBUPRENORPHINE(BUP) + Faldaprevir(FDV) on Day 9 vs. NORBUPRENORPHINE(BUP) alone on Day 1p-value: 0.315290% CI: [74.85, 167.67]ANOVA
Primary
Norbuprenorphine: Geometric Mean Steady-state Cmax on Day 1 and on Day 9.
These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state.
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | Norbuprenorphine: Geometric Mean Steady-state Cmax on Day 1 and on Day 9. | NORBUPRENORPHINE with FDV (Day 9) | 3690 [pg/mL] | Geometric Coefficient of Variation 91.9 |
| Methadone Group | Norbuprenorphine: Geometric Mean Steady-state Cmax on Day 1 and on Day 9. | NORBUPRENORPHINE alone (Day 1) | 2770 [pg/mL] | Geometric Coefficient of Variation 126 |
Comparison: NORBUPRENORPHINE(BUP) + Faldaprevir(FDV) on Day 9 vs. NORBUPRENORPHINE(BUP) alone on Day 1p-value: 0.618890% CI: [93.32, 189.16]ANOVA
Primary
R-methadone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9.
These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours.
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | R-methadone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9. | R-methadone with FDV (Day 9) | 6990 [ng*h/mL] | Geometric Coefficient of Variation 31.7 |
| Methadone Group | R-methadone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9. | R-methadone alone (Day 1) | 5920 [ng*h/mL] | Geometric Coefficient of Variation 37.2 |
Comparison: Methadone(MTD) + Faldaprevir(FDV) on Day 9 vs. Methadone(MTD) alone on Day 1p-value: 0.163890% CI: [107.06, 130.32]ANOVA
Primary
R-methadone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9.
These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | R-methadone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9. | R-methadone with FDV (Day 9) | 235 [ng/mL] | Geometric Coefficient of Variation 36.8 |
| Methadone Group | R-methadone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9. | R-methadone alone (Day 1) | 210 [ng/mL] | Geometric Coefficient of Variation 39.4 |
Comparison: Methadone(MTD) + Faldaprevir(FDV) on Day 9 vs. Methadone(MTD) alone on Day 1p-value: 0.060390% CI: [99.243, 125.922]ANOVA
Primary
R-methadone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9.
These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state.
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | R-methadone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9. | R-methadone with FDV (Day 9) | 393 [ng/ml] | Geometric Coefficient of Variation 29.8 |
| Methadone Group | R-methadone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9. | R-methadone alone (Day 1) | 345 [ng/ml] | Geometric Coefficient of Variation 33.3 |
Comparison: Methadone(MTD) + Faldaprevir(FDV) on Day 9 vs. Methadone(MTD) alone on Day 1p-value: 0.039190% CI: [104.812, 124.164]ANOVA
Primary
S-methadone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9
These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours.
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | S-methadone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9 | S-methadone with FDV (Day 9) | 7610 [ng*h/ml] | Geometric Coefficient of Variation 39.3 |
| Methadone Group | S-methadone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9 | S-methadone alone (Day 1) | 6470 [ng*h/ml] | Geometric Coefficient of Variation 41.5 |
Comparison: S-Methadone(MTD) + Faldaprevir(FDV) on Day 9 vs. S-Methadone(MTD) alone on Day 1p-value: 0.142490% CI: [106.89, 129.5]ANOVA
Primary
S-methadone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9
These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | S-methadone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9 | S-methadone with FDV (Day 9) | 231 [ng/mL] | Geometric Coefficient of Variation 46.3 |
| Methadone Group | S-methadone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9 | S-methadone alone (Day 1) | 207 [ng/mL] | Geometric Coefficient of Variation 48.8 |
Comparison: S-Methadone(MTD) + Faldaprevir(FDV) on Day 9 vs. S-Methadone(MTD) alone on Day 1p-value: 0.048890% CI: [99.577, 124.888]ANOVA
Primary
S-methadone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9
These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state.
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug and had evaluable data for at least one observation for at least one primary endpoint. Subjects considered to be not evaluable, if the subject had a protocol deviation relevant to relative bioavailability. Or experienced emesis and vomiting at or before two times median tmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Methadone Group | S-methadone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9 | S-methadone with FDV (Day 9) | 474 [ng/mL] | Geometric Coefficient of Variation 36.6 |
| Methadone Group | S-methadone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9 | S-methadone alone (Day 1) | 425 [ng/mL] | Geometric Coefficient of Variation 34.9 |
Comparison: S-Methadone(MTD) + Faldaprevir(FDV) on Day 9 vs. S-Methadone(MTD) alone on Day 1p-value: 0.036790% CI: [100.42, 123.715]ANOVA
Secondary
Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline
The OOWS is conducted by a trained independent examiner for either the presence or absence of the following symptoms during a 10 minute observation period at designated times during the trial. The minimum possible OOWS score is 0 and the maximum possible score is 13. Objective criteria: Yawning, Rhinorrhoea, Piloerection, perspiration, lacrimation, mydriasis, hot and cold flushes, restlessness, vomiting, tremors, anxiety, muscle twitches, abdominal cramps. Higher score indicates increasing severity of opiate withdrawal syndrome.
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 2 | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 3 | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 4 (N=15,18) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 5 (N=15,18) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 6 (N=15,18) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 7 (N=15,15) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 8 (N=15,15) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 9 (N=15,15) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 10 (N=15,15) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 11 (N=15,15) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 12 (N=15,15) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | End of Treatment (EOT) (N=14,16) | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 12 (N=15,15) | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 2 | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 8 (N=15,15) | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 3 | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 11 (N=15,15) | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 4 (N=15,18) | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 9 (N=15,15) | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 5 (N=15,18) | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | End of Treatment (EOT) (N=14,16) | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 6 (N=15,18) | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 10 (N=15,15) | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline | Day 7 (N=15,15) | 0.0 units on a scale |
Comparison: Pearson correlation of trough concentrations of R-methadone and OOWS95% CI: [-0.189801, 0.16864]
Comparison: Pearson correlation of change from baseline for trough concentrations of R-methadone and OOWS95% CI: [-0.287471, 0.092062]
Comparison: Pearson correlation of trough concentrations of S-methadone and OOWS95% CI: [-0.209893, 0.148238]
Comparison: Pearson correlation of change from baseline for trough concentrations of S-methadone and OOWS95% CI: [-0.189172, 0.194156]
Comparison: Pearson correlation of trough concentrations of Buprenorphine and OOWS95% CI: [-0.214505, 0.149733]
Comparison: Pearson correlation of change from baseline for trough concentrations of Buprenorphine and OOWS95% CI: [-0.404929, 0.135425]
Comparison: Pearson correlation of trough concentrations of norbuprenorphine and OOWS95% CI: [-0.240578, 0.136305]
Comparison: Pearson correlation of change from baseline for trough concentrations of norbuprenorphine and OOWS95% CI: [-0.344024, 0.163687]
Comparison: Pearson correlation of trough concentrations of naloxone and OOWS
Secondary
Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline
The SOWS is a subjective scale self-evaluated by the subject. The SOWS shows items reflecting the common motor, autonomic, gastrointestinal, musculo-skeletal, and psychic symptoms of opiate withdrawal. Subjects are instructed to rate each symptom on a scale of 0 to 4 (0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely) at designated times \[c.f. Section 3.1\]. The minimum possible SOWS score is 0, the maximum 64. The following subjective criteria are answered by the subject using the scale below: 1) I feel anxious, 2) I feel like yawning 3) I am perspiring, 4) My eyes are watering, 5) My nose is running, 6) I have goose flesh, 7) I am shaking 8) I have hot flushes, 9) I have cold flushes, 10) My bones and muscles ache, 11) I feel restless, 12) I feel nauseous, 13) I feel like vomiting, 14) My muscles twitch, 15) I have cramps in my stomach, 16) I feel like shooting up now. Higher score indicates increasing severity of opiate withdrawal syndrome.
Time frame: 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
Population: This set included all subjects who took at least one dose of study drug.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 3 | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 8 (N=15,15) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 5 (N=15,18) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 9 (N=15,15) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 10 (N=15,15) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 2 | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 11 (N=15,15) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 6 (N=15,18) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 12 (N=15,15) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 4 (N=15,18) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | End of Treatment (EOT) (N=14,16) | 0.0 units on a scale |
| Methadone Group | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 7 (N=15,15) | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | End of Treatment (EOT) (N=14,16) | -1.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 2 | -1.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 3 | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 4 (N=15,18) | 0.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 5 (N=15,18) | -0.5 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 6 (N=15,18) | -0.5 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 7 (N=15,15) | -1.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 8 (N=15,15) | -1.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 10 (N=15,15) | -1.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 11 (N=15,15) | -1.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 12 (N=15,15) | -1.0 units on a scale |
| Buprenorphine/Naloxone (Suboxone) | Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline | Day 9 (N=15,15) | -1.0 units on a scale |
Comparison: Pearson correlation of trough concentrations of R-methadone and SOWS95% CI: [-0.13275, 0.224946]
Comparison: Pearson correlation of change from baseline for trough concentrations of R-methadone and SOWS95% CI: [-0.547072, -0.222288]
Comparison: Pearson correlation of trough concentrations of S-methadone and SOWS95% CI: [-0.069336, 0.284848]
Comparison: Pearson correlation of change from baseline for trough concentrations of S-methadone and SOWS95% CI: [-0.34787, 0.025107]
Comparison: Pearson correlation of trough concentrations of Buprenorphine and SOWS95% CI: [-0.17016, 0.194417]
Comparison: Pearson correlation of change from baseline for trough concentrations of Buprenorphine and SOWS95% CI: [-0.253932, 0.29696]
Comparison: Pearson correlation of trough concentrations of norbuprenorphine and SOWS95% CI: [-0.24392, 0.132819]
Comparison: Pearson correlation of change from baseline for trough concentrations of norbuprenorphine and SOWS95% CI: [-0.218159, 0.293233]
Comparison: Pearson correlation of trough concentrations of naloxone and SOWS