TMC278-TiDP6-C154: Evaluation of the Possible Influence of Omeprazole Intake - and the pH Increase in the Stomach Triggered by Omeprazole Intake - on the Blood Levels of TMC278 in Healthy Volunteers
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to investigate the extent by which intake of 20 mg once daily
      (q.d.) omeprazole influences the levels of TMC278 in the blood after intake of 25 mg q.d..
      This study also investigates - in case levels of TMC278 are reduced when co-administered with
      omeprazole - whether a double dose of TMC278 (50 mg q.d.) or a separation of intake of both
      drugs by 12 hours may circumvent a decrease of TMC278 levels in the blood below the clinical
      effective concentration. Omeprazole is prescribed to reduce the production of gastric acid.
      Since TMC278 requires gastric acid to be properly dissolved and taken up in the blood
      circulation, intake of omeprazole has an influence on the levels of TMC278 in the blood
      circulation. This effect has been revealed in a previously conducted clinical trial, using
      the combination of 150 mg TMC278 q.d. and 20 mg q.d. omeprazole. The currently proposed study
      will also further explore the relationship between the levels of TMC278 in the blood at
      several time points and the acidity of the stomach. Also the short-term safety and
      tolerability of co-administration of omeprazole 20 mg q.d. and TMC278 25 mg q.d. will be
      assessed.
    

Detailed description: 
      This is an open label study, which means that all parties including the study doctor, the
      healthy volunteer and the sponsor plus his designees will know at all times which treatment
      the volunteer is in. This is a 4-way cross over trial, which means that every volunteer will
      be sequentially subjected to 4 different treatments.There are 4 treatment sequences defined:
      ABCD, BDAC, CADB and DCBA. Treatment sessions are organized in such a way that between
      successive intakes of TMC278 a period of 14 days is respected. Treatment A is the reference,
      showing the levels of TMC278 in blood without any intake of omeprazole. These data points
      will be compared with blood levels of TMC278 when TMC278 is being administered 1.5 hours
      after intake of omeprazole (Treatment B) or with blood levels of TMC278 when being
      administered 12 hours after intake of omeprazole (Treatment C). Treatment B will be the
      comparator of Treatment D, in order to reveal whether doubling the dose of TMC278 (50 mg q.d.
      used in Treatment D) can circumvent the reduction of TMC278 levels when being co-administered
      with omeprazole, if applicable. In each session, an extensive investigation of the levels of
      TMC278 in the blood circulation is planned. Levels of TMC278 will be assessed at 16 different
      time points, i.e. before administration of TMC278, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48,
      72, 120 and 168 hours after intake of TMC278. During all treatments, the acidity in the
      stomach (called intragastric pH) will be monitored during a 24-hour period on the day of
      TMC278 intake. Standard Safety assessments (blood biochemistry and haematology, urine
      analysis, ECG, pulse rate and blood pressure) will be performed on Day1, 2 and 8 in Treatment
      A and on Day-5, 1, 2, 8 in Treatment B, C and D. Treatment A: 25mg TMC278 in the morning of
      Day1; Treatment B: 25mg TMC278 in the morning of Day1 and 20mg omeprazole in the morning from
      Day-5 through Day2 (7 days in total); Treatment C: same as treatment B, but omeprazole is
      taken in the evening; Treatment D: same as treatment B, but 50mg omeprazole is taken instead
      of 25mg. All intakes are oral. In Treatment B, C and D, the intake of omeprazole is witnessed
      by site staff on Days -5, -3, -2 and -1
    

Intervention name(s): TMC278; Omeprazole
Intervention type(s): Drug
Intervention MeSH terms: Rilpivirine; Omeprazole
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: TMC278-TiDP6-C154; TMC278-C154; TMC278; Healthy volunteers; omeprazole; proton pump inhibitor; HIV