Potential Influence of Pantoprazole on the Pharmacokinetics of Pritelivir
Condition: HSV Infection
MeSH terms: Herpes Simplex
Intervention: Pritelivir; ESO and pritelivir
Intervention description: oral administration; oral administration
Intervention MeSH terms: Pritelivir
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Sequence for all subjects:
Treatment 1: single dose of 100 mg PTV followed by Wash out period (4weeks) followed by Treatment 2: single dose of 100 mg PTV Day 1 and 40 mg/day ESO from Day -3 to Day 1
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      To investigate the effect of esomeprazole (ESO) on the pharmacokinetics of pritelivir (PTV),
      and to investigate the safety and tolerability of PTV.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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;

          2. 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.

          3. 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.

          4. 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.

          5. 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.

          6. 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.

          7. Subject agreed to pharmacogenetic blood sampling.

          8. 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.

          9. 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;

         10. 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:

          1. History or current evidence of clinically relevant allergies or idiosyncrasy to drugs
             or food

          2. History of allergic reactions to any active or inactive ingredient(s) of the trial
             medication(s)

          3. 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

          4. History of malignancy

          5. Resting pulse rate after 5 minutes in supine position at Screening and Day -1 of
             Treatment Period 1: <45 or >100 beats per minute (bpm), if out of range, up to one
             repeat assessment was allowed

          6. Resting blood pressure after 5 minutes in supine position at Screening and Day -1 of
             Treatment Period 1: systolic blood pressure <90 or >145 mmHg diastolic blood pressure
             <40 or >95 mmHg, if out of range, up to one repeat assessment was allowed

          7. ECG abnormalities of clinical relevance (eg, QTc according to Fridericia: QTc >450 ms
             in males and >470 ms in females; PR ≥220 ms)

          8. Febrile or infectious illness within 5 days prior to administration of Investigational
             Medicinal Product

          9. Clinically relevant abnormalities in clinical chemical, hematological or any other
             laboratory variables

         10. Chronic or clinically relevant acute infections

         11. Diagnosed to be COVID-19 positive by polymerase chain reaction (PCR) testing
             (SARS-CoV-2 RT-PCR positive) of a respiratory specimen (preferably a nasopharyngeal
             swab) on Day -2 of Treatment Period 1

         12. Subject was lactating or breastfeeding

         13. Use of any medication (incl. over-the-counter [OTC] medication) within 2 weeks before
             first drug administration or within less than 10 times the elimination half-life of
             the respective drug, or anticipated concomitant medication during the treatment
             periods. Use of hormonal contraceptives was allowed. Single intake of a drug may have
             been accepted if judged by the Investigators to have no clinical relevance and no
             relevance for the trial objectives. Limited amounts of acetaminophen were allowed to
             treat painful intercurrent adverse events (eg, headache, migraine).

         14. Consumption of any (eg, CYP1A2, CYP3A4) enzyme inducing or inhibiting aliments and
             beverages (eg, but not limited to broccoli, Brussels sprout, grapefruit, grapefruit
             juice, Seville orange, star fruit, tonic water, bitter lemon etc.) within 2 weeks
             prior to the Screening (Pre-trial examination)

         15. Consumption of methylxanthine-containing beverages or food (coffee, tea, cola,
             chocolate, "powerdrinks") from 24 hours before PTV dosing on Day 1 until release from
             the clinic on Day 5 of each period

         16. Consumption of alcohol and tobacco products within 48 hours prior to admission to the
             clinic until discharge of each period

         17. Vegetarian diet or other dietary habits which would have precluded the subject's
             acceptance of standardized meals

         18. Diseases or surgery of the gastrointestinal tract which may have interfered with drug
             absorption (note: this was not applicable for minor abdominal surgery such as eg,
             appendectomy and herniotomy)

         19. Receipt of any Investigational Medicinal Product (IMP) within a time period equal to
             10 half-lives of the product, if known, or a minimum of 30 days prior to trial drug
             administration.

         20. Blood donation or loss of 550 mL or more within the last 30 days before start of
             Screening (Pre-trial examination)

         21. Smoking of more than 10 cigarettes/cigars/pipes per Day and/or inability to refrain
             from smoking during confinement

         22. Intake of more than 12 units of alcohol per week (one unit of alcohol equals
             approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits)

         23. Had any finding that, in the view of the Investigator, would have compromised the
             subject's safety requirements