Potential Influence of Esomeprazole on the Pharmacokinetics of Pritelivir

Inclusion Criteria

• Subjects had to have the ability to understand and sign written informed consent, which had to be obtained prior to any trial-related procedures being completed;
• Healthy male and female subjects of any ethnic origin, aged between 18 and 45 years (inclusive) assessed as healthy based on a pre-trial examination including medical history, physical examination, blood pressure, pulse rate, electrocardiogram (ECG) assessment, and clinical laboratory results.
• Female subjects of non-childbearing potential had to be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks prior to Screening) or postmenopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone (FSH) in the postmenopausal range at Screening based on the central laboratory's ranges.
• Female subjects of childbearing potential (ie, ovulating, premenopausal, and not surgically sterile) and all male subjects had to use a medically accepted contraceptive regimen during their participation in the trial and for 90 days after the last administration of trial drug. Medically accepted contraceptive methods were defined as those with 90% or greater efficacy.

Acceptable methods of contraception for male subjects enrolled in the trial included the following:

• Condoms with spermicide.
• Surgical sterilization of the subject at least 26 weeks prior to Screening (vasectomy).

Acceptable methods of contraception for female subjects enrolled in the trial included the following, (the subject had to choose two of the following [a single barrier method alone or abstinence alone was not acceptable]):

• Condoms with spermicide.
• Intrauterine device for at least 12 weeks prior to Screening.
• Hormonal contraception (oral, implant, injection, ring, or patch) for at least 12 weeks prior to Screening.
• Diaphragm used in combination with spermicide.
• Male subjects had to agree to abstain from sperm donation and not plan to father a child (including sperm donation) through 90 days after administration of the last dose of trial drug.
• In women: a negative serum beta-human chorionic gonadotropin (β-HCG) test at Screening and negative urine β-HCG test at Admission in each Treatment Period.
• Subject agreed to pharmacogenetic blood sampling.
• Normal body weight as evidenced by a Body Mass Index (BMI) ≥18.0 and ≤32.0 kg/m2, and a body weight ≥50.0 kg at Screening.
• Subjects had to have a negative test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), and human immunodeficiency virus (HIV) at Screening;
• Subjects had to have negative urine tests for drugs of abuse (metamphetamines, amphetamines, 3,4-Methylendioxyamphetamin (MDMA), barbiturates, benzodiazepines, cannabinoids, opioids, cocaine and tricyclic antidepressants) and negative breath alcohol tests at Screening and Admission in each Treatment Period.

Exclusion criteria

• History or current evidence of clinically relevant allergies or idiosyncrasy to drugs or food
• History of allergic reactions to any active or inactive ingredient(s) of the trial medication(s)
• History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrinological, metabolic, neurological, psychiatric, or other disease suspected to influence pharmacokinetics or safety of PTV
• History of malignancy
• Resting pulse rate after 5 minutes in supine position at Screening and Day -1 of Treatment Period 1: 100 beats per minute (bpm), if out of range, up to one repeat assessment was allowed
• Resting blood pressure after 5 minutes in supine position at Screening and Day -1 of Treatment Period 1: systolic blood pressure 145 mmHg diastolic blood pressure 95 mmHg, if out of range, up to one repeat assessment was allowed
• ECG abnormalities of clinical relevance (eg, QTc according to Fridericia: QTc >450 ms in males