Hepatitis C, ChronicPhase 1NCT01525628

Drug Drug Interaction Study Between BI 201335 and BI 207127 in Chronic Hepatitis C Infected Patients

A Phase 1 study testing midazolam, BI 201335 and tenofovir in people with Hepatitis C, Chronic, run by Boehringer Ingelheim at 16 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

To evaluate the drug-drug interactions between BI 201335 and BI 207127 as well as their combined effect on CYP probe drug substrates and on tenofovir and raltegravir in treatment naive or prior treatment relapse patients with chronic hepatitis C infection. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Hepatitis C, Chronic
What is being tested?: midazolam, BI 201335 and tenofovir
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 72 participants
Where: 16 sitesin 3 countries
Study dates: Apr 2012to Oct 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Chronic hepatitis C genotype 1 infection, diagnosed at least 6 months prior to screening
Treatment naive or confirmed prior treatment relapse or partial response following treatment with interferon and ribavirin
Age 18 to 70 years
HCV RNA (Hepatitis C Virus RiboNucleic Acid) = 1,000 IU/mL at screening
Liver biopsy or fibroscan to exclude cirrhosis

Who cannot join

Hepatitis C Virus (HCV) infection of mixed genotype; Hepatitis B Virus (HBV) or Human Immunodeficiency Virus (HIV) co-infection
Evidence of acute or chronic liver disease due to causes other than chronic HCV infection,
Decompensated liver disease, or history of decompensated liver disease,
Body weight < 40 or > 125 kg,
Clinical evidence of significant or unstable cardiovascular disease, chronic pulmonary disease, history or evidence of retinopathy or clinically significant ophthalmological disorder
Pre-existing psychiatric condition that could interfere with the subject's participation in and completion of the study

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Laboratory parameters disorders (thalassemia major, sickle cell anemia or glucose 6 phosphate dehydrogenase deficit)
Hemoglobin < 12 g/dL for women and < 13 g/dL for men
Patients who have been previously treated with at least one dose of any antiviral or immunomodulatory drug other than interferon alfa or ribavirin for acute or chronic HCV infection

Trial locations and contacts

16 sites in 3 countries.

Country

City, postcode or hospital

16 sites in 3 countries

Canada7 sites

1241.27.0100 Boehringer Ingelheim Investigational Site
London, Ontario
1241.27.0500 Boehringer Ingelheim Investigational Site
Montreal, Quebec
1241.27.0300 Boehringer Ingelheim Investigational Site
Ottawa, Ontario
1241.27.0200 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia
1241.27.0600 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia
1241.27.0700 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia
1241.27.0400 Boehringer Ingelheim Investigational Site
Victoria, British Columbia

Other trials in Canada

United States5 sites

1241.27.0006 Boehringer Ingelheim Investigational Site
La Mesa, California
1241.27.0004 Boehringer Ingelheim Investigational Site
Marlton, New Jersey
1241.27.0003 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania
1241.27.0005 Boehringer Ingelheim Investigational Site
Rockville, Maryland
1241.27.0001 Boehringer Ingelheim Investigational Site
Salt Lake City, Utah

Other trials in United States

Germany4 sites

1241.27.4907 Boehringer Ingelheim Investigational Site
Cologne
1241.27.4901 Boehringer Ingelheim Investigational Site
Frankfurt am Main
1241.27.4903 Boehringer Ingelheim Investigational Site
Leipzig
1241.27.4906 Boehringer Ingelheim Investigational Site
Mainz

Other trials in Germany

About this study

Official title: A Multi-centre, Open Label, Parallel Group Trial to Evaluate the Pharmacokinetic Interactions Between BI 207127 (600 mg t.i.d. or 600 mg b.i.d.) and BI 201335 (120 mg q.d.) Given in Combination With Ribavirin for 24 Weeks, and Their Combined Effect on the Pharmacokinetics of Tenofovir, Raltegravir, Caffeine (the Probe Drug Substrate for CYP1A2), Tolbutamide (the Probe Drug Substrate for CYP2C9) and Midazolam (the Probe Drug Substrate for CYP3A4) in Treatment naïve Patients and Prior Treatment Relapse or Partial Responder Patients With Genotype 1 Chronic Hepatitis C Infection

Conditions: Hepatitis C, Chronic
Being tested: midazolam, BI 201335, tenofovir, caffeine, tolbutamide
Medical subject headings: Hepatitis C, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

midazolamDrug
CYP3A probe drug
BI 201335Drug
HCV protease inhibitor
tenofovirDrug
nucleoside analogue
caffeineDrug
CYP1A2 probe drug
tolbutamideDrug
CYP2C9 probe drug
tolbutamideDrug
CYP2C9 probe drug
midazolamDrug
CYP3A probe drug
caffeineDrug
CYP1A2 probe drug
pegylated interferonDrug
HCV treatment
BI 201335Drug
HCV protease inhibitor
BI 201335Drug
HCV protease inhibitor
BI 207127Drug
HCV polymerase inhibitor
BI 207127Drug
HCV polymerase inhibitor
BI 201335Drug
HCV protease inhibitor
BI 207127Drug
HCV polymerase inhibitor
ribavirinDrug
HCV treatment
ribavirinDrug
HCV treatment
ribavirinDrug
HCV treatment
pegylated interferonDrug
HCV treatment
ribavirinDrug
HCV treatment
caffeineDrug
CYP1A2 probe drug
tolbutamideDrug
CYP2C9 probe drug
BI 207127Drug
HCV polymerase inhibitor
midazolamDrug
CYP3A probe drug
BI 201335Drug
HCV protease inhibitor
BI 207127Drug
HCV polymerase inhibitor
ribavirinDrug
HCV treatment

Study groups in NCT01525628
Study group	Role	What they receive
Group A	Experimental	Effect of BI 207127 on BI 201335, the effect of BI 201335 and dual oral direct acting antiviral (DAAs) on caffeine, tolbutamide and midazolam Receives: Drug: tolbutamide; Drug: midazolam; Drug: caffeine; Drug: BI 201335; Drug: pegylated interferon; Drug: BI 207127; Drug: ribavirin
Group B	Experimental	Effect of BI 201335 on BI 207127, the effect of BI 207127 and metabolites and dual oral DAAs on caffeine, tolbutamide and midazolam Receives: Drug: BI 201335; Drug: caffeine; Drug: tolbutamide; Drug: pegylated interferon; Drug: BI 207127; Drug: ribavirin; Drug: midazolam
Group C	Experimental	Effect of Dual oral DAAs on tenofovir Receives: Drug: tenofovir; Drug: BI 207127; Drug: ribavirin; Drug: BI 201335
Group D	Experimental	Effect of BI 201335 and BI 207127 at 600 mg b.i.d. on caffeine, tolbutamide and midazolam Receives: Drug: midazolam; Drug: BI 201335; Drug: BI 207127; Drug: ribavirin; Drug: caffeine; Drug: tolbutamide
Group E	Experimental	Effect of BI 201335 and BI 207127 on raltegravir Receives: Drug: BI 201335; Drug: ribavirin; Drug: BI 207127

What is being measured

The primary outcome is the main question the study is designed to answer.

Cmax of Faldaprevir (BI 201335)
Maximum concentration of an analyte in plasma
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
C24hr of Faldaprevir (BI 201335)
Concentration of an analyte in plasma at 24 hours
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Cmax of Deleobuvir (BI 207127)
Maximum concentration of an analyte in plasma
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
C6hr of Deleobuvir (BI 207127)
Concentration of an analyte in plasma at 6 hours
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
AUC 0-6hr of Deleobuvir (BI 207127)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
Maximum concentration of an analyte in plasma
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
Concentration of an analyte in plasma at 6 hours
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Cmax of Deleobuvir Reduction Metabolite CD 6168
Maximum concentration of an analyte in plasma
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
C6hr of Deleobuvir Reduction Metabolite CD 6168
Concentration of an analyte in plasma at 6 hours
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
Maximum concentration of an analyte in plasma
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
Concentration of an analyte in plasma at 6 hours
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Cmax of Caffeine
Maximum concentration of an analyte in plasma
Measured: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
AUC 0-infinity of Caffeine
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Measured: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Cmax of Tolbutamide
Maximum concentration of an analyte in plasma
Measured: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
AUC 0-infinity of Tolbutamide
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Measured: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Cmax of Midazolam
Maximum concentration of an analyte in plasma
Measured: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
AUC 0-infinity of Midazolam
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Measured: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Cmax of 1-OH-Midazolam (1-hydroxy-midazolam)
Maximum concentration of an analyte in plasma
Measured: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Measured: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Cmax of Tenofovir
Maximum concentration of an analyte in plasma.
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
C24hr of Tenofovir
Concentration of an analyte in plasma at 24 hours.
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
AUC 0-24hr of Tenofovir
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours.
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
Cmax of Raltegravir
Maximum concentration of an analyte in plasma.
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
C12hr of Raltegravir
Concentration of an analyte in plasma at 12 hours.
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
AUC 0-12hr of Raltegravir
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 12 hours.
Measured: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17

Secondary outcomes (1)

Number of Participants With Sustained Virological Response (SVR12)
Sustained virologic response (SVR12): Plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level <25 IU/mL(international units per millilitre) undetectable at 12 weeks after the end of treatment. SVR12 was analyzed in a descriptive manner using frequency of participants who achieved SVR12.
Measured: 12 weeks post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2012Oct 2014

First posted3 Feb 2012 (estimated)
Study startApr 2012
Primary completionDec 2013
Study completionOct 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hepatitis C, ChronicStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 72 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01525628
Sponsor's protocol ID: 1241.27
Other IDs: 2012-004102-10
Status last verified: May 2016
First submitted: 1 Feb 2012
Last updated: 10 Jun 2016
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic

All Hepatitis C, Chronic trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-centre, Open Label, Parallel Group Trial to Evaluate the Pharmacokinetic Interactions Between BI 207127 (600 mg t.i.d. or 600 mg b.i.d.) and BI 201335 (120 mg q.d.) Given in Combination With Ribavirin for 24 Weeks, and Their Combined Effect on the Pharmacokinetics of Tenofovir, Raltegravir, Caffeine (the Probe Drug Substrate for CYP1A2), Tolbutamide (the Probe Drug Substrate for CYP2C9) and Midazolam (the Probe Drug Substrate for CYP3A4) in Treatment naïve Patients and Prior Treatment Relapse or Partial Responder Patients With Genotype 1 Chronic Hepatitis C Infection
ClinicalTrials.gov ID: NCT01525628
Acronym / sponsor ID: 1241.27
Conditions: Hepatitis C, Chronic
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 72 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Apr 2012
Primary completion: Dec 2013 (actual)
Study completion: Oct 2014 (actual)
First posted: 3 Feb 2012 (estimated)
Results: Posted 10 Jun 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Group A	Experimental	Drug: tolbutamide, Drug: midazolam, Drug: caffeine, Drug: BI 201335, Drug: pegylated interferon, Drug: BI 207127, Drug: ribavirinEffect of BI 207127 on BI 201335, the effect of BI 201335 and dual oral direct acting antiviral (DAAs) on caffeine, tolbutamide and midazolam
Group B	Experimental	Drug: BI 201335, Drug: caffeine, Drug: tolbutamide, Drug: pegylated interferon, Drug: BI 207127, Drug: ribavirin, Drug: midazolamEffect of BI 201335 on BI 207127, the effect of BI 207127 and metabolites and dual oral DAAs on caffeine, tolbutamide and midazolam
Group C	Experimental	Drug: tenofovir, Drug: BI 207127, Drug: ribavirin, Drug: BI 201335Effect of Dual oral DAAs on tenofovir
Group D	Experimental	Drug: midazolam, Drug: BI 201335, Drug: BI 207127, Drug: ribavirin, Drug: caffeine, Drug: tolbutamideEffect of BI 201335 and BI 207127 at 600 mg b.i.d. on caffeine, tolbutamide and midazolam
Group E	Experimental	Drug: BI 201335, Drug: ribavirin, Drug: BI 207127Effect of BI 201335 and BI 207127 on raltegravir

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Chronic hepatitis C genotype 1 infection, diagnosed at least 6 months prior to screening
Treatment naive or confirmed prior treatment relapse or partial response following treatment with interferon and ribavirin
Age 18 to 70 years
HCV RNA (Hepatitis C Virus RiboNucleic Acid) = 1,000 IU/mL at screening
Liver biopsy or fibroscan to exclude cirrhosis

Key exclusion criteria (9 listed)

Hepatitis C Virus (HCV) infection of mixed genotype; Hepatitis B Virus (HBV) or Human Immunodeficiency Virus (HIV) co-infection
Evidence of acute or chronic liver disease due to causes other than chronic HCV infection,
Decompensated liver disease, or history of decompensated liver disease,
Body weight < 40 or > 125 kg,
Clinical evidence of significant or unstable cardiovascular disease, chronic pulmonary disease, history or evidence of retinopathy or clinically significant ophthalmological disorder

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
midazolamCYP3A probe drug	Drug	Group D
BI 201335HCV protease inhibitor	Drug	Group B
tenofovirnucleoside analogue	Drug	Group C
caffeineCYP1A2 probe drug	Drug	Group B
tolbutamideCYP2C9 probe drug	Drug	Group B
tolbutamideCYP2C9 probe drug	Drug	Group A
midazolamCYP3A probe drug	Drug	Group A
caffeineCYP1A2 probe drug	Drug	Group A
pegylated interferonHCV treatment	Drug	Group B
BI 201335HCV protease inhibitor	Drug	Group D
BI 201335HCV protease inhibitor	Drug	Group E
BI 207127HCV polymerase inhibitor	Drug	Group C
BI 207127HCV polymerase inhibitor	Drug	Group D
BI 201335HCV protease inhibitor	Drug	Group A
BI 207127HCV polymerase inhibitor	Drug	Group B
ribavirinHCV treatment	Drug	Group B
ribavirinHCV treatment	Drug	Group C
ribavirinHCV treatment	Drug	Group E
pegylated interferonHCV treatment	Drug	Group A
ribavirinHCV treatment	Drug	Group D
caffeineCYP1A2 probe drug	Drug	Group D
tolbutamideCYP2C9 probe drug	Drug	Group D
BI 207127HCV polymerase inhibitor	Drug	Group A
midazolamCYP3A probe drug	Drug	Group B
BI 201335HCV protease inhibitor	Drug	Group C
BI 207127HCV polymerase inhibitor	Drug	Group E
ribavirinHCV treatment	Drug	Group A

Primary outcome

Cmax of Faldaprevir (BI 201335)
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Maximum concentration of an analyte in plasma
C24hr of Faldaprevir (BI 201335)
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Concentration of an analyte in plasma at 24 hours
Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours
Cmax of Deleobuvir (BI 207127)
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Maximum concentration of an analyte in plasma
C6hr of Deleobuvir (BI 207127)
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Concentration of an analyte in plasma at 6 hours
AUC 0-6hr of Deleobuvir (BI 207127)
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Maximum concentration of an analyte in plasma
C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Concentration of an analyte in plasma at 6 hours
AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Cmax of Deleobuvir Reduction Metabolite CD 6168
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Maximum concentration of an analyte in plasma
C6hr of Deleobuvir Reduction Metabolite CD 6168
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Concentration of an analyte in plasma at 6 hours
AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Maximum concentration of an analyte in plasma
C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Concentration of an analyte in plasma at 6 hours
AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Cmax of Caffeine
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Maximum concentration of an analyte in plasma
AUC 0-infinity of Caffeine
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Cmax of Tolbutamide
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Maximum concentration of an analyte in plasma
AUC 0-infinity of Tolbutamide
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Cmax of Midazolam
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Maximum concentration of an analyte in plasma
AUC 0-infinity of Midazolam
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Cmax of 1-OH-Midazolam (1-hydroxy-midazolam)
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Maximum concentration of an analyte in plasma
AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam)
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Cmax of Tenofovir
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
Maximum concentration of an analyte in plasma.
C24hr of Tenofovir
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
Concentration of an analyte in plasma at 24 hours.
AUC 0-24hr of Tenofovir
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours.
Cmax of Raltegravir
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
Maximum concentration of an analyte in plasma.
C12hr of Raltegravir
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
Concentration of an analyte in plasma at 12 hours.
AUC 0-12hr of Raltegravir
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 12 hours.

1 secondary outcome

Number of Participants With Sustained Virological Response (SVR12)
Time frame: 12 weeks post treatment

Results and safety

Results posted to the registry on 10 Jun 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group A	16	14
Group B	19	14
Group C	16	11
Group D	14	10
Group E	7	4

Primary outcome: Cmax of Faldaprevir (BI 201335)

Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Group A n = 16	Group B n = 19
Day 9 (N=15,0)	3520 (54.8)	NA (NA)
Day 17 (N=14,14)	8780 (47.5)	9950 (51.0)
Day 66 (N=13,15)	4410 (48.7)	6690 (78.8)

Group A: Ratio of gmeans Day 17 vs. Day 9 (%): 251.37 (90% CI 205.54 to 307.43), p = 1.0000, ANOVA
Group A: Ratio of gmeans Day 66 vs. Day 9 (%): 131.30 (90% CI 105.40 to 163.57), p = 0.6514, ANOVA

Population analysed: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.

Primary outcome: C24hr of Faldaprevir (BI 201335)

Measure	Group A n = 16	Group B n = 19
Day 9 (N=15,0)	983 (65.5)	NA (NA)
Day 17 (N=14,19)	3670 (90.4)	5410 (91.6)
Day 66 (N=13,14)	1140 (107)	2580 (135)

Group A: Ratio of gmeans Day 17 vs. Day 9 (%): 381.11 (90% CI 317.01 to 458.19), p = 1.0000, ANOVA
Group A: Ratio of gmeans Day 66 vs. Day 9 (%): 123.65 (90% CI 94.66 to 161.51), p = 0.4718, ANOVA

Primary outcome: Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours

Measure	Group A n = 16	Group B n = 19
Day 9 (N=15,0)	45600 (54.5)	NA (NA)
Day 17 (N=14,19)	138000 (62.1)	173000 (60.8)
Day 66 (N=13,15)	56200 (58.2)	97300 (114)

Group A: Ratio of gmeans Day 17 vs. Day 9 (%): 306.45 (90% CI 250.93 to 374.26), p = 1.0000, ANOVA
Group A: Ratio of gmeans Day 66 vs. Day 9 (%): 129.85 (90% CI 104.26 to 161.71), p = 0.6185, ANOVA

Primary outcome: Cmax of Deleobuvir (BI 207127)

Measure	Group A n = 16	Group B n = 19
Day 9 (N=0, 17)	NA (NA)	10900 (85.3)
Day 17 (N=14, 19)	27000 (64.6)	31400 (45.8)
Day 66 (N=13, 15)	10100 (78.2)	16000 (100)

Group B: Ratio of gmeans Day 17 vs. Day 9 (%): 286.01 (90% CI 228.51 to 357.97), p = 1.0000, ANOVA
Group B: Ratio of gmeans Day 66 vs. Day 9 (%): 150.45 (90% CI 106.81 to 211.91), p = 0.8210, ANOVA

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From first drug administration until last drug administration plus 28 days, up to 28 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group A	0 of 16 (0%)	16 of 16 (100%)	Not reported
Group B	0 of 19 (0%)	19 of 19 (100%)	Not reported
Group C	1 of 16 (6.3%)	16 of 16 (100%)	Not reported
Group D	2 of 14 (14.3%)	14 of 14 (100%)	Not reported
Group E	0 of 7 (0%)	5 of 7 (71.4%)	Not reported

Limitations and caveats (from the sponsor): BI decided to stop the further development of the interferon-free combination therapy for Hepatitis C in December 2013 so the recruitment was stopped after 7 patients had entered Group E also PK analyses for Groups C to E were not performed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

16 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing midazolam, BI 201335 and tenofovir in people with Hepatitis C, Chronic, run by Boehringer Ingelheim at 16 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Canada, United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cmax of Faldaprevir (BI 201335) (time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.). The study lists 29 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01525628.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2016.