A Fixed-Sequence, Drug-Drug Interaction Study Between Multiple Oral Doses of Inarigivir Soproxil and a Single Oral Dose of Midazolam in Healthy Subjects

F-Star

Status and phase: Completed; Phase 1

Conditions: Drug Interaction Potentiation

Treatments: Drug: Inarigivir; Drug: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT03493698

SBP-9200-HBV-202

2018-000607-16 (EudraCT Number)

Details and patient eligibility

About

This is a single center, open-label, fixed sequence study to investigate the effect of multiple oral dosing of Inarigivir Soproxil and a single oral dose of Midazolam in Healthy Subjects

Enrollment: 17 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Gender : male or female
2. Age : 18-55 years, inclusive, at screening
3. Body mass index (BMI) : 18.0-30.0 kg/m2, inclusive, at screening
4. Status : healthy subjects
5. At screening, females must be non-pregnant and non-lactating, or of non-childbearing potential (either surgically sterilized or physiologically incapable of becoming pregnant, or at least 1 year post-menopausal [amenorrhoea duration of 12 consecutive months]); non-pregnancy will be confirmed for all females by a serum pregnancy test conducted at screening, and a urine pregnancy test at each admission and at follow-up
6. Female subjects of childbearing potential, with a fertile male sexual partner, must agree to use adequate contraception from screening until 90 days after the follow-up visit. Adequate contraception is defined as using a non-hormonal intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm or cervical cap, or a condom; please note that hormonal contraceptives are not allowed. Also, total abstinence, in accordance with the lifestyle of the subject, is acceptable
7. Male subjects, if not surgically sterilized, must agree to use adequate contraception and not donate sperm from admission to the clinical research center until 90 days after the follow-up visit. Adequate contraception for the male subject (and his female partner) is defined as using hormonal contraceptives or an intrauterine device, combined with at least 1 of the following forms of contraception: a diaphragm or cervical cap, or a condom. Also, total abstinence, in accordance with the lifestyle of the subject is acceptable
8. All prescribed medication, including hormonal contraceptives for female subjects, must have been stopped at least 30 days prior to admission to the clinical research center
9. All over-the-counter medication, vitamin preparations and other food supplements, or herbal medications (eg, St. John's Wort) must have been stopped at least 14 days prior to admission to the clinical research center. An exception is made for paracetamol, which is allowed up to admission to the clinical research center
10. Ability and willingness to abstain from alcohol, methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, energy drinks) and grapefruit (juice) from 72 hours prior to admission to the clinical research center
11. Good physical and mental health on the basis of medical history, physical examination, clinical laboratory, electrocardiogram (ECG) and vital signs, as judged by the PI
12. Willing and able to sign the ICF

Exclusion criteria

1. Employee of PRA or the Sponsor
2. History of relevant drug and/or food allergies
3. Using tobacco products within 60 days prior to the first drug administration
4. History of alcohol abuse or drug addiction (including soft drugs like cannabis products)
5. Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines [including ecstasy], cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants and alcohol) at screening and admission to the clinical research center
6. Average intake of more than 24 units of alcohol per week (1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits)
7. Positive screen for hepatitis B surface antigen (HBsAg), anti-HCV antibodies or anti-human immunodeficiency virus (HIV) 1 and 2 antibodies
8. Participation in a drug study within 60 days prior to the first drug administration in the current study. Participation in more than 4 other drug studies in the 12 months prior to the first drug administration in the current study
9. Donation or loss of more than 100 mL of blood within 60 days prior to the first drug administration. Donation or loss of more than 1.5 liters of blood (for male subjects) / more than 1.0 liters of blood (for female subjects) in the 10 months prior to the first drug administration in the current study
10. Significant and/or acute illness within 5 days prior to the first drug administration that may impact safety assessments, in the opinion of the PI

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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17 participants in 3 patient groups

Treatment A: Midazolam

Experimental group

Description:

All subjects will receive a single oral dose of 2 mg Midazolam on Day 1

Treatment:

Drug: Midazolam

Treatment B and C: Inarigivir

Experimental group

Description:

All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3, Day 6-18

Treatment:

Drug: Inarigivir

Treatment D: Inarigivir with Midazolam

Experimental group

Description:

All subjects will receive a single oral dose of 400 mg Inarigivir coa administered with a single oral dose of 2 mg Midazolam on Day 19

Treatment:

Drug: Midazolam

Drug: Inarigivir