Drug Drug Interaction of BI 201335 and Tenofovir

Study Overview
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Brief Summary
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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.

Official Title
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Effect of Multiple Dosing With 240 mg BID BI 201335 on the Steady State Pharmacokinetics of 300mg QD Tenofovir and Effect of Multiple Dosing With 300mg QD Tenofovir on Steady State BI 201335 Pharmacokinetics in Healthy Male and Female Volunteers

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: tenofovir/BI 201335


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy males and female subjects and according to medical history, including the physical examination, vital signs (blood pressure, pulse rate), 12-lead electrocardiogram and clinical laboratory tests; all with acceptable findings. Age =18 to =55 years Weighing at least 50 kg, and body mass index >=18.5 and BMI <=29.9 kg/m2 (Body Mass Index). Volunteers must not leave the research unit, during the entire length of the study and must be willing to comply with the protocol and complete all study-related activities. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sequence 1<br>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) | Drug: tenofovir/BI 201335<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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. | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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. |