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The objective of this study is to evaluate the drug-drug interaction potential between BI 201335 and concomitantly administered tenofovir which is used in treatment regimens for HIV infection and/or Hepatitis B infection. Results of this study will serve as a basis for guidance of dose adjustments or other precautionary measures when BI201335 and tenofovir are coadministered.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| sequence 1 | Experimental | tenofovir medium dose once daily (qd) for first 15 days; BI 201335 medium dose twice daily (bid) on days 8 through day 22 (morning dose on day 22 only) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tenofovir/BI 201335 | Drug | tenofovir medium dose once daily (qd) for first 15 days; BI 201335 medium dose twice daily (bid) on days 8 through 22 with last dose on morning of day 22 |
| Measure | Description | Time Frame |
|---|---|---|
| Steady-state Pharmacokinetics of AUC0-24 of Tenofovir on Day 7 and on Day 15 | Area under the concentration-time curve (AUC) of the analyte in plasma over the time interval 0-24 hours, at steady state. | 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00, 168:00 hours on day 7 and 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15 |
| Steady-state Pharmacokinetics of Cmax of Tenofovir on Day 7 and on Day 15 | Maximum measured concentration of analyte in plasma (Cmax), at steady state. | 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00, 168:00 hours on day 7 and 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00. 192:00 hours on day 15 |
| Steady-state Pharmacokinetics of C24hr of Tenofovir on Day 7 and on Day 15 | Measured concentration of the analyte in plasma at 24 h (C24hr) after dosing, at steady state. | 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00, 168:00 hours on day 7 and 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15 |
| Steady-state Pharmacokinetics of AUC0-12 of Faldaprevir on Day 15 and on Day 22 | Area under the concentration-time curve (AUC) of the analyte in plasma over the time interval 0-12 hours, at steady state. | 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15 and 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00 hours on day 22 |
| Steady-state Pharmacokinetics of Cmax of Faldaprevir on Day 15 and Day 22 | Maximum measured concentration of analyte in plasma (Cmax), at steady state. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Drug Related Adverse Events During the Trial | Outcome data are the numbers of subjects with investigator defined drug-related AEs | From drug administration up to 32 days. |
| Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Safety Laboratory Tests and 12-lead ECG |
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Inclusion criteria:
Exclusion criteria:
Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance, as assessed by the investigator.
Active diseases of the gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, musculoskeletal, immunologic, rheumatologic, hormonal, neurological system, clinically relevant electrolyte disorders or bleeding disorders that require current medical treatment.
Diseases of the central nervous system or psychiatric disorders.
History of photosensitivity or recurrent rash.
History of orthostatic hypotension, fainting spells or blackouts.
Chronic or clinically relevant acute infections.
History of allergy/hypersensitivity (including drug allergy) which is deemed relevant.
Intake of drugs with a long half-life >24:00 hours within at least one month or less than ten half lives of the respective drug before enrollment in the study (with the exception of hormonal contraceptives).
Use of any drugs which might influence the results of the trial up to 7 days prior to enrolment as nutraceuticals and herbal remedies that would interfere with either the absorption, distribution or metabolism of BI 201335 NA, or that prolong the QT/QTc interval.
Use of any investigational drug within 30 days prior to enrollment; or the planned use of any investigational drug during the course of the current study.
Smoking (>10 cigarettes or >3 cigars or >3 pipes/day)
Inability to abstain from smoking more than 3 cigarettes/day during the period of dosing with study medication.
Drug and alcohol abuse (>60g/day).
Blood donation (more than 100 mL within four weeks prior to administration or during the trial).
Excessive physical activities within one week prior to administration or during the trial.
Any laboratory value outside the reference range that is of clinical relevance at screening, according to the judgment of the investigator, and in consultation with the clinical monitor.
Known elevated liver enzymes in past with any compound (experimental or marketed).
Concomitant administration of any food product known to alter P450 enzyme activity such as grapefruit juice, Seville oranges, St. John's Wort.
Concomitant administration of oral contraceptives (subjects who stopped oral contraceptives at least 7 days prior to Day 1 may be included.
Inadequate venous access.
A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTcF, or QTcB interval >450 ms).
Infection with hepatitis B (HBV), or hepatitis C virus (HCV),
Positive test for HIV-1 or HIV-2. For women of child bearing potential (WOCBP)
Pregnancy or planning to become pregnant within 2 months of study completion
Positive pregnancy test at screening visit
No proof of sterilization, or not willing or unable to consistently use an acceptable method of double barrier contraception including IUD, or diaphragm with spermicidal cream/jelly and condoms for male partner, during and up to 3 months after completion/termination of the trial.
Lactation period with active breastfeeding from time of screening to 30 days after end of trial visit.
For male subjects
No proof of sterilization, or not willing or unable to consistently use an acceptable method of double barrier contraception including a condom each time and female partner of child bearing potential consistently uses oral birth control pills, or an IUD, or a diaphragm with spermicidal cream/jelly). Male subjects must not father a child from administration of the first dose and up to 3 months after the last dose of study medication.
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1220.50.0001 Boehringer Ingelheim Investigational Site | Buffalo | New York | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | All Participants | tenofovir medium dose (300mg) once daily (qd, oral) for first 15 days; Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (300mg) twice daily (bid) on days 9 through day 22 (morning dose on day 22 only) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treat. Period 1 (Tenofovir) |
| |||||||||||||
| Treat. Period 2 (Tenofovir/Faldaprevir) |
| |||||||||||||
| Treat. Period 3 (Faldaprevir) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | tenofovir medium dose (300mg) once daily (qd, oral) for first 15 days; Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (300mg) twice daily (bid) on days 9 through day 22 (morning dose on day 22 only) |
| 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 | Steady-state Pharmacokinetics of AUC0-24 of Tenofovir on Day 7 and on Day 15 | Area under the concentration-time curve (AUC) of the analyte in plasma over the time interval 0-24 hours, at steady state. | All participants from the pharmacokinetic analysis set (PK set), including all subjects who were documented to have taken at least one dose of trial medication (treated set) who provided evaluable data for at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00, 168:00 hours on day 7 and 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15 |
|
From drug administration up to 32 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 | Tenofovir | tenofovir medium dose (300mg) once daily (qd) (day 1 to 7) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Oral herpes | Infections and infestations | MEDDRA 14.0 | 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 |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15 and 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00 hours on day 22 |
| Steady-state Pharmacokinetics of C12hr of Faldaprevir on Day 15 and on Day 22 | Measured concentration of the analyte in plasma at 12 h (C12hr) after dosing, at steady state. | 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15 and 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00 hours on day 22 |
Clinical relevant abnormalities for physical examination, vital signs, safety laboratory tests and 12-lead ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Preferred term of relevant AE: Presyncope |
| From drug administration up to 32 days. |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Tenofovir/Faldaprevir | tenofovir medium dose (300mg) once daily (qd) (day 8 to 15); Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (240mg) twice daily (bid) on days 9 through day 15 |
| OG002 | Faldaprevir | Faldaprevir medium dose (240mg) twice daily (bid) (day 16 to 22, last dose on morning of day 22) |
|
|
|
| Primary | Steady-state Pharmacokinetics of Cmax of Tenofovir on Day 7 and on Day 15 | Maximum measured concentration of analyte in plasma (Cmax), at steady state. | All participants from the pharmacokinetic analysis set (PK set), including all subjects in the treated set who provided evaluable data for at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00, 168:00 hours on day 7 and 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00. 192:00 hours on day 15 |
|
|
|
|
| Primary | Steady-state Pharmacokinetics of C24hr of Tenofovir on Day 7 and on Day 15 | Measured concentration of the analyte in plasma at 24 h (C24hr) after dosing, at steady state. | All participants from the pharmacokinetic analysis set (PK set), including all subjects in the treated set who provided evaluable data for at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00, 168:00 hours on day 7 and 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15 |
|
|
|
|
| Primary | Steady-state Pharmacokinetics of AUC0-12 of Faldaprevir on Day 15 and on Day 22 | Area under the concentration-time curve (AUC) of the analyte in plasma over the time interval 0-12 hours, at steady state. | All participants from the pharmacokinetic analysis set (PK set), including all subjects in the treated set who provided evaluable data for at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15 and 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00 hours on day 22 |
|
|
|
|
| Primary | Steady-state Pharmacokinetics of Cmax of Faldaprevir on Day 15 and Day 22 | Maximum measured concentration of analyte in plasma (Cmax), at steady state. | All participants from the pharmacokinetic analysis set (PK set), including all subjects in the treated set who provided evaluable data for at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15 and 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00 hours on day 22 |
|
|
|
|
| Primary | Steady-state Pharmacokinetics of C12hr of Faldaprevir on Day 15 and on Day 22 | Measured concentration of the analyte in plasma at 12 h (C12hr) after dosing, at steady state. | All participants from the pharmacokinetic analysis set (PK set), including all subjects in the treated set who provided evaluable data for at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 168:00, 168:30, 169:00, 169:30, 170:00, 172:00, 174:00, 176:00, 178:00, 180:00, 192:00 hours on day 15 and 144:00, 144:30, 145:00, 145:30, 146:00, 147:00, 148:00, 150:00, 152:00, 156:00 hours on day 22 |
|
|
|
|
| Secondary | Number of Patients With Drug Related Adverse Events During the Trial | Outcome data are the numbers of subjects with investigator defined drug-related AEs | All subjects who were dispensed study medication and were documented to have taken at least one dose of study drug were included in the safety evaluation (treated set). | Posted | Number | participants | From drug administration up to 32 days. |
|
|
|
| Secondary | Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Safety Laboratory Tests and 12-lead ECG | Clinical relevant abnormalities for physical examination, vital signs, safety laboratory tests and 12-lead ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Preferred term of relevant AE: Presyncope | All subjects who were dispensed study medication and were documented to have taken at least one dose of study drug were included in the safety evaluation (treated set). | Posted | Number | participants | From drug administration up to 32 days. |
|
|
|
| 0 |
| 16 |
| 1 |
| 16 |
| EG001 | Tenofovir/Faldaprevir | tenofovir medium dose (300mg) once daily (qd) (day 8 to 15); Faldaprevir starting dose of 480mg and evening dose of 240mg on day 8; medium dose (240mg) twice daily (bid) on days 9 through day 15 | 0 | 16 | 16 | 16 |
| EG002 | Faldaprevir | Faldaprevir medium dose (240mg) twice daily (bid) (day 16 to 22, last dose on morning of day 22) | 0 | 16 | 10 | 16 |
| Decreased appetite | Metabolism and nutrition disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Ocular icterus | Eye disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Malaise | General disorders | MEDDRA 14.0 | Systematic Assessment |
|
| Pain | General disorders | MEDDRA 14.0 | 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.
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |