The purpose of the study is to investigate the effect of inarigivir on the absorption, distribution and elimination of midazolam in order to assess to what extent inarigivir may possibly change the pharmacokinetics of other drugs when given with…
ID
Source
Brief title
Condition
- Other condition
- Hepatic and hepatobiliary disorders
Synonym
Health condition
Hepatitis B
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the effect of steady-state oral inarigivir on the single dose
pharmacokinetics (PK) of oral midazolam in healthy subjects.
Secondary outcome
To evaluate the safety and tolerability of a single oral dose of midazolam, a
single oral dose of inarigivir, and multiple oral doses of inarigivir
administered without and with a single oral dose of midazolam in healthy
subjects.
To assess the PK of inarigivir after single and multiple oral doses in healthy
subjects.
Exploratory:
To evaluate the pharmacodynamics (PD) following single and multiple oral doses
of inarigivir in healthy subjects.
Background summary
Inarigivir is a new compound that may eventually be used for the treatment of
chronic hepatitis B. Hepatitis B is a worldwide common infection of the liver
caused by a virus. If it does not heal spontaneously and evolves into chronic
hepatitis, there is no effective treatment. If the infection has not healed
spontaneously after 6 months, it is a chronic hepatitis B virus infection.
Currently, there is no treatment to cure chronic hepatitis B virus infection.
However, the virus can be suppressed with drugs currently available.
Inarigivir is selectively active within cells infected with the hepatitis B
virus. Inarigivir binds certain proteins in the cell resulting in the
inhibition of replication of the virus and in addition the induction of
antiviral defense.
Study objective
The purpose of the study is to investigate the effect of inarigivir on the
absorption, distribution and elimination of midazolam in order to assess to
what extent inarigivir may possibly change the pharmacokinetics of other drugs
when given with inarigivir in the future. In addition, the pharmacokinetics of
single and multiple doses of inarigivir will be investigated. It will also be
investigated how safe inarigivir is and how well inarigivir is tolerated.
Further, the effect of inarigivir on certain blood markers, will be
investigated.
Study design
This is an open-label, fixed-sequence, drug-drug interaction study in 16
healthy male or female volunteers.
The actual study will consist of 1 period during which the volunteer will stay
in the research center (location UMCG) for 21 days (20 nights).
Day 1 is the first day of administration of the study compound. The volunteer
is expected at the research center at 14:00 h in the afternoon prior to the day
of first administration of the study compound. The volunteer will leave the
research center on Day 20 of the study.
Planned treatments:
Day 1: a single dose of 2 milligrams (mg) midazolam on Day 1 (Day 1 is the
first day of administration of the study compound)
Day 3: a single dose of 400 mg inarigivir (4 tablets of 100 mg each) on Day 3
Day 6 to Day 17: a single dose of 400 mg inarigivir (4 tablets of 100 mg each)
each day for 12 days (from Day 6 to Day 17)
Day 18: a single dose of 400 mg inarigivir (4 tablets of 100 mg each) will be
administered together with a single dose of 2 mg midazolam on Day 18
Intervention
During the study the volunteer will receive a single dose and multiple doses of
inarigivir and 2 single doses of midazolam. Inarigivir will be given as oral
tablets and midazolam will be given as an oral solution. Inarigivir will be
administered with 240 milliliters (mL) of tap water. Midazolam will be
administered using a syringe.
Planned treatments:
Day 1: a single dose of 2 milligrams (mg) midazolam on Day 1 (Day 1 is the
first day of administration of the study compound)
Day 3: a single dose of 400 mg inarigivir (4 tablets of 100 mg each) on Day 3
Day 6 to Day 17: a single dose of 400 mg inarigivir (4 tablets of 100 mg each)
each day for 12 days (from Day 6 to Day 17)
Day 18: a single dose of 400 mg inarigivir (4 tablets of 100 mg each) will be
administered together with a single dose of 2 mg midazolam on Day 18
Study burden and risks
One clinical study with inarigivir has been completed and another one is still
ongoing. In the completed study, inarigivir was administered as single doses up
to 800 mg and multiple doses up to 900 mg for 7 days in patients with hepatitis
C virus infection. After both single and multiple doses, inarigivir was well
tolerated up to the highest dose level. The most frequently reported side
effects following multiple doses of inarigivir were headache, diarrhea, nausea,
increased liver enzymes and insomnia. The increased liver enzymes were
attributed to the hepatitis C virus infection, not to inarigivir.
The single 2 mg oral dose of midazolam is a standard dose used in drug-drug
interaction studies and is less than the usual therapeutic dose of 10 to 20 mg.
The dose is expected to be safe and well tolerated even when given together
with inarigivir.
Midazolam has a boxed warning from the FDA because it can cause breathing
difficulties. Midazolam has been associated with severe breathing
difficulties, including slowed breathing, inability to breathe, airway
obstruction and low oxygen most often when used together with other central
nervous system depressants (for example, pain medications). A significant
decrease in the rate of breathing can cause death if not treated correctly.
Pain, minor bleedings, bruising, possibly an infection.
South Street 86
Hopkinton MA 01748
US
South Street 86
Hopkinton MA 01748
US
Listed location countries
Age
Inclusion criteria
-Healthy male or female subjects
-18-55 years, inclusive, at screening
-BMI 18.0-30.0 kg/m2, inclusive, at screening
-Females must be non-pregnant, non-lactating and of non childbearing potential
Exclusion criteria
Suffering from hepatitis B, hepatitis C, cancer or HIV/AIDS. In case of participation in another drug study within 90 days before the start of this study or being a blood donor within 60 days from the start of the study. In case of donating more than 1.5 liters of blood in the 10 months prior the start of this study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-000607-16-NL |
| CCMO | NL65122.056.18 |