A Drug-Drug Interaction Study to Evaluate the Effect of Vapendavir on the Pharmacokinetics of Midazolam in Healthy Male and Female Volunteers

A Phase 1, Randomized, Open-Label Study to Evaluate the Effect of Vapendavir (BTA798) on the Pharmacokinetics of Orally Administered Midazolam, a CYP3A4 Substrate, in Healthy Male and Female Volunteers

The primary aim of this Phase 1 study is to evaluate the effect of vapendavir daily doses of 528 mg daily (QD) and 264 mg twice daily (BID) on the pharmacokinetic (PK) profile of midazolam, a cytochrome (CYP) 3A4 substrate. Additionally, the effect of midazolam on the PK profile of vapendavir, a PK profile comparison of vapendavir in males and females, as well as the safety of vapendavir will also be assessed.

Inclusion Criteria:

• Must be male or female between 18 and 55 years of age (inclusive) with BMI between 18 and 30 kg/m2 (inclusive), and weight ≥50 kg at the time of screening;
• Capable of giving written informed consent;
• Subject is able to understand and comply with the protocol requirements, instructions and restrictions;
• Healthy on the basis of physical examination, medical history, medication usage, vital signs (VS), electrocardiograms (ECGs), and clinical laboratory tests;
• Female subjects who are not post-menopausal for at least 2 years or surgically sterile with complete hysterectomy or bilateral oophorectomy and male subjects who are not surgically sterile via vasectomy, must agree to use a double barrier method of birth control, such as a condom plus spermicidal agent (foam/gel/film/cream/suppository); and
• Female subjects must not be breastfeeding or pregnant.

Exclusion Criteria:

• Positive results for Hepatitis B, Hepatitis C, or HIV;
• Frequent use (defined as > 5 times/day) of tobacco products, including cigarettes, cigars, chewing tobacco;
• A medical history of significant hematological, gastrointestinal, respiratory, renal, hepatic, cerebrovascular, immunologic, psychiatric or cardiovascular disease or event;
• Current or recent respiratory infection (defined as within 14 days of first study visit participation)
• Presence or history of significant allergy;
• Clinically significant abnormalities noted on ECG;
• Screening vital signs representing sustained elevated systolic blood pressure <90 mmHg or >140 mmHg, and/or diastolic blood pressure <55 mmHg or >90 mmHg.
• Presence of significant gastrointestinal abnormalities such as diarrhea or constipation;
• Safety laboratory abnormalities noted at screening which are clinically significant
• Current or defined history of abuse of alcohol or illicit drugs;
• A positive pregnancy test at screening;
• Poor vein access or fear of venipuncture or sight of blood; and
• Regular consumption of alcohol defined as either > 2 units (glass or shot) of alcoholic beverages per day or > 14 units per week.