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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methadone group | Active Comparator | patients on stable methadone therapy (at least 30 days) up to a maximum of 180mg per day |
|
| Buprenorphine | Active Comparator | patients on stable buprenorphine/naloxone therapy (at least 30 days) up to a maximum dose of 24mg/6mg per day. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 201335 | Drug | BI 201335 for 9 days |
| |
| BI 201335 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
| 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. | 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 |
| 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 | 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 |
| 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. | 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 |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion criteria:
Exclusion criteria:
any other significant medical illness of clinical significance.
history of rash or photosensitivity
chronic or acute infections including HIV, hepatitis B and hepatitis C.
history of allergy considered significant for this study
intake of any other medications except for methadone or buprenorphine/naloxone.
QTc on electrocardiogram (ECG) > 470.
use of any other investigational drug within 30 days of the study.
drug or alcohol abuse (other than the defined opioid maintenance therapy with either methadone or buprenorphine/naloxone)
blood donation of more than 100mL within four weeks of the trial.
excessive physical activities one week prior to and during the trial.
any clinically relevant laboratory value.
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.
inadequate venous access
For women of childbearing potential:
pregnancy or planning to become pregnant within 3 months of the trial
positive pregnancy test at screening visit
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.
lactation with active breastfeeding from screening up to 30 days after last study visit.
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1220.57.0001 Boehringer Ingelheim Investigational Site | Atlanta | Georgia | United States | |||
| 1220.57.0002 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25385094 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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): Oral dose of BI 201335(faldaprevir) 480 mg on day 2 and 240 mg twice daily for days 3 to 9. |
| FG001 | 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): Oral dose of BI 201335(faldaprevir) 480 mg on day 2 and 240 mg twice daily for days 3 to 9. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
This set included all subjects who were dispensed study medication and were documented to have taken at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Buprenorphine/Naloxone (Suboxone) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [ng*h/mL] | 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 |
|
30 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytosis | Blood and lymphatic system disorders | MEDDRA 15.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| ID | Term |
|---|---|
| C552340 | faldaprevir |
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| Drug |
BI 201335 for 9 days |
|
| 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 |
| 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 | 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 |
| 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. | 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 |
| 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. | 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 |
| 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 | 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 |
| 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. | 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 |
| 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. | 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 |
| 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 | 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 |
| 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. | 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 |
| 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. | 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 |
| 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 | 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 |
| 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 |
| 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. | 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 |
| Overland Park |
| Kansas |
| United States |
| 1220.57.0003 Boehringer Ingelheim Investigational Site | Salt Lake City | Utah | United States |
| Withdrawal by Subject |
|
| Lost to Follow-up |
|
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.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [ng/ml] | 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 |
|
|
|
|
| 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 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [ng/mL] | 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 |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [ng*h/ml] | 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 |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [ng/mL] | 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 |
|
|
|
|
| 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 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [ng/mL] | 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 | 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. | This set included all subjects who took at least one dose of study drug. | Posted | Median | Full Range | units on a scale | 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 |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [pg*h/ml] | 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 |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [pg/ml] | 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 |
|
|
|
|
| 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 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [pg/mL] | 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 | 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. | This set included all subjects who took at least one dose of study drug. | Posted | Median | Full Range | units on a scale | 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 |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [pg*h/ml] | 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 |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [pg/mL] | 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 |
|
|
|
|
| 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 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [pg/mL] | 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 |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [pg*h/ml] | 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 |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [pg/mL] | 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 |
|
|
|
|
| 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 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | [pg/mL] | 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 |
|
|
|
| 0 |
| 15 |
| 12 |
| 15 |
| EG001 | 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. | 0 | 19 | 18 | 19 |
| Conjunctivitis | Eye disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Dry eye | Eye disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Fatigue | General disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Drug-induced liver injury | Hepatobiliary disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MEDDRA 15.1 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MEDDRA 15.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MEDDRA 15.1 | Systematic Assessment |
|
| Pruritus generalised | Skin and subcutaneous tissue disorders | MEDDRA 15.1 | Systematic Assessment |
|
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights..
| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
No formal testing, investigation of relative bioavailability |
No formal testing, investigation of relative bioavailability |
No formal testing, investigation of relative bioavailability |
No formal testing, investigation of relative bioavailability |
No formal testing, investigation of relative bioavailability |
| Day 4 (N=15,18) |
|
| Day 5 (N=15,18) |
|
| Day 6 (N=15,18) |
|
| Day 7 (N=15,15) |
|
| Day 8 (N=15,15) |
|
| Day 9 (N=15,15) |
|
| Day 10 (N=15,15) |
|
| Day 11 (N=15,15) |
|
| Day 12 (N=15,15) |
|
| End of Treatment (EOT) (N=14,16) |
|
| Pearson Correlation Coefficient |
| -0.10188 |
| 2-Sided |
| 95 |
| -0.287471 |
| 0.092062 |
| No |
| Superiority or Other |
| Pearson correlation of trough concentrations of S-methadone and OOWS | Pearson Correlation Coefficient | -0.03198 | 2-Sided | 95 | -0.209893 | 0.148238 | No | Superiority or Other |
| Pearson correlation of change from baseline for trough concentrations of S-methadone and OOWS | Pearson Correlation Coefficient | 0.00260 | 2-Sided | 95 | -0.189172 | 0.194156 | No | Superiority or Other |
| Pearson correlation of trough concentrations of Buprenorphine and OOWS | Pearson Correlation Coefficient | -0.03364 | 2-Sided | 95 | -0.214505 | 0.149733 | No | Superiority or Other |
| Pearson correlation of change from baseline for trough concentrations of Buprenorphine and OOWS | Pearson Correlation Coefficient | -0.14703 | 2-Sided | 95 | -0.404929 | 0.135425 | No | Superiority or Other |
| Pearson correlation of trough concentrations of norbuprenorphine and OOWS | Pearson Correlation Coefficient | -0.05431 | 2-Sided | 95 | -0.240578 | 0.136305 | No | Superiority or Other |
| Pearson correlation of change from baseline for trough concentrations of norbuprenorphine and OOWS | Pearson Correlation Coefficient | -0.09727 | 2-Sided | 95 | -0.344024 | 0.163687 | No | Superiority or Other |
| Pearson correlation of trough concentrations of naloxone and OOWS | Pearson Correlation Coefficient | 0.36105 | Confidence interval is not provided due to sparse data. There was only 1 patient for this analysis. | No | Superiority or Other |
No formal testing, investigation of relative bioavailability |
No formal testing, investigation of relative bioavailability |
No formal testing, investigation of relative bioavailability |
| Day 4 (N=15,18) |
|
| Day 5 (N=15,18) |
|
| Day 6 (N=15,18) |
|
| Day 7 (N=15,15) |
|
| Day 8 (N=15,15) |
|
| Day 9 (N=15,15) |
|
| Day 10 (N=15,15) |
|
| Day 11 (N=15,15) |
|
| Day 12 (N=15,15) |
|
| End of Treatment (EOT) (N=14,16) |
|
| Pearson Correlation Coefficient |
| -0.39865 |
| 2-Sided |
| 95 |
| -0.547072 |
| -0.222288 |
| No |
| Superiority or Other |
| Pearson correlation of trough concentrations of S-methadone and SOWS | Pearson Correlation Coefficient | 0.11175 | 2-Sided | 95 | -0.069336 | 0.284848 | No | Superiority or Other |
| Pearson correlation of change from baseline for trough concentrations of S-methadone and SOWS | Pearson Correlation Coefficient | -0.16815 | 2-Sided | 95 | -0.347870 | 0.025107 | No | Superiority or Other |
| Pearson correlation of trough concentrations of Buprenorphine and SOWS | Pearson Correlation Coefficient | 0.01260 | 2-Sided | 95 | -0.170160 | 0.194417 | No | Superiority or Other |
| Pearson correlation of change from baseline for trough concentrations of Buprenorphine and SOWS | Pearson Correlation Coefficient | 0.02352 | 2-Sided | 95 | -0.253932 | 0.296960 | No | Superiority or Other |
| Pearson correlation of trough concentrations of norbuprenorphine and SOWS | Pearson Correlation Coefficient | -0.05787 | 2-Sided | 95 | -0.243920 | 0.132819 | No | Superiority or Other |
| Pearson correlation of change from baseline for trough concentrations of norbuprenorphine and SOWS | Pearson Correlation Coefficient | 0.04052 | 2-Sided | 95 | -0.218159 | 0.293233 | No | Superiority or Other |
| Pearson correlation of trough concentrations of naloxone and SOWS | Pearson Correlation Coefficient | 0.92231 | Confidence interval is not provided due to sparse data. There was only 1 patient for this analysis. | No | Superiority or Other |
No formal testing, investigation of relative bioavailability |
No formal testing, investigation of relative bioavailability |
No formal testing, investigation of relative bioavailability |
No formal testing, investigation of relative bioavailability |
No formal testing, investigation of relative bioavailability |