Phase 1
N=72
Drug Drug Interaction Study Between BI 201335 and BI 207127 in Chronic Hepatitis C Infected Patients
Hepatitis C, Chronic
Bottom Line
View on ClinicalTrials.gov: NCT01525628 ↗Enrolled (actual)
72
Serious AEs
4.2%
Results posted
Jun 2016
Primary outcome: Primary: Cmax of Faldaprevir (BI 201335) — 3520; NA; 8780; 9950 ng/mL — p=1.0000
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- midazolam (Drug); BI 201335 (Drug); tenofovir (Drug); caffeine (Drug); tolbutamide (Drug); pegylated interferon (Drug); BI 207127 (Drug); ribavirin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Boehringer Ingelheim
- Primary completion
- Dec 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cmax of Faldaprevir (BI 201335) |
3520; NA; 8780; 9950; 4410; 6690 | 1.0000 |
| PRIMARY C24hr of Faldaprevir (BI 201335) |
983; NA; 3670; 5410; 1140; 2580 | 1.0000 |
| PRIMARY Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours |
45600; NA; 138000; 173000; 56200; 97300 | 1.0000 |
| PRIMARY Cmax of Deleobuvir (BI 207127) |
NA; 10900; 27000; 31400; 10100; 16000 | 1.0000 |
| PRIMARY C6hr of Deleobuvir (BI 207127) |
NA; 5800; 17900; 20800; 5080; 10100 | 1.0000 |
| PRIMARY AUC 0-6hr of Deleobuvir (BI 207127) |
NA; 41100; 119000; 135000; 36200; 59200 | 1.0000 |
| PRIMARY Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) |
NA; 5620; 12700; 20200; 3790; 6550 | 1.0000 |
| PRIMARY C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) |
NA; 4330; 11200; 17500; 2740; 5780 | 1.0000 |
| PRIMARY AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) |
NA; 24300; 61800; 98800; 15000; 27600 | 1.0000 |
| PRIMARY Cmax of Deleobuvir Reduction Metabolite CD 6168 |
NA; 3040; 8520; 12400; 4510; 8880 | 1.0000 |
| PRIMARY C6hr of Deleobuvir Reduction Metabolite CD 6168 |
NA; 2250; 6980; 10200; 3360; 7460 | 1.0000 |
| PRIMARY AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168 |
NA; 13300; 41700; 62200; 19300; 39100 | 1.0000 |
| PRIMARY Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) |
NA; 203; 596; 1130; 386; 806 | 1.0000 |
| PRIMARY C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) |
NA; 159; 508; 962; 295; 712 | 1.0000 |
| PRIMARY AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) |
NA; 893; 2980; 5700; 1620; 3510 | 1.0000 |
| PRIMARY Cmax of Caffeine |
5170; 5340; 4890; 7220; 4830; 6530 | 0.0500 |
| PRIMARY AUC 0-infinity of Caffeine |
54900; 77500; 42100; 142000; 71900; 170000 | 0.1037 |
| PRIMARY Cmax of Tolbutamide |
152000; 170000; 146000; 158000; 130000; 126000 | 0.0015 sig |
| PRIMARY AUC 0-infinity of Tolbutamide |
1940000; 2220000; 1800000; 1940000; 1520000; 1410000 | 0.0005 sig |
| PRIMARY Cmax of Midazolam |
21.1; 23.8; 29.9; 29.8; 31.9; 28.8 | 0.9749 |
| PRIMARY AUC 0-infinity of Midazolam |
79.7; 107; 117; 130; 127; 140 | 0.9941 |
| PRIMARY Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) |
5.57; 6.68; 6.50; 6.52; 6.46; 5.02 | 0.1519 |
| PRIMARY AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) |
23.6; 26.0; 24.2; 28.5; 23.5; 22.8 | 0.1159 |
| PRIMARY Cmax of Tenofovir |
— | — |
| PRIMARY C24hr of Tenofovir |
— | — |
| PRIMARY AUC 0-24hr of Tenofovir |
— | — |
| PRIMARY Cmax of Raltegravir |
— | — |
| PRIMARY C12hr of Raltegravir |
— | — |
| PRIMARY AUC 0-12hr of Raltegravir |
— | — |
| SECONDARY Number of Participants With Sustained Virological Response (SVR12) |
13; 13; 11; 10; 3 | — |
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.
Eligibility Criteria
Inclusion criteria
- 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
Exclusion criteria
- 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 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
- 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
Data sourced from ClinicalTrials.gov (NCT01525628). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.