Drug Interaction PotentiationPhase 1NCT03493698

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

A Phase 1 study testing Midazolam and Inarigivir in people with Drug Interaction Potentiation, run by F-star Therapeutics, Inc. at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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 Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Drug Interaction Potentiation
What is being tested?: Midazolam and Inarigivir
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 17 participants
Where: 1 siteNetherlands
Study dates: 7 May 2018to 27 Aug 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Gender : male or female
Age : 18-55 years, inclusive, at screening
Body mass index (BMI) : 18.0-30.0 kg/m2, inclusive, at screening
Status : healthy subjects
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
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

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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
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
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
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
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
Willing and able to sign the ICF

Who cannot join

Employee of PRA or the Sponsor
History of relevant drug and/or food allergies
Using tobacco products within 60 days prior to the first drug administration
History of alcohol abuse or drug addiction (including soft drugs like cannabis products)
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
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)

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Positive screen for hepatitis B surface antigen (HBsAg), anti-HCV antibodies or anti-human immunodeficiency virus (HIV) 1 and 2 antibodies
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
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
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 locations and contacts

1 site in 1 country.

Netherlands1 site

University Medical Center Groningen
Groningen

Other trials in Netherlands

About this study

Official title: A Phase 1, Open-label, Fixed-Sequence, Drug-Drug Interaction Study Between Multiple Oral Doses of Inarigivir Soproxil and a Single Oral Dose of Midazolam in Healthy Subjects

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

Conditions: Drug Interaction Potentiation
Being tested: Midazolam, Inarigivir

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MidazolamDrug
Midazolam
InarigivirDrug
Also called Inarigivir Soproxil, SB 9200
Inarigivir

Study groups in NCT03493698
Study group	Role	What they receive
Treatment A: Midazolam	Experimental	All subjects will receive a single oral dose of 2 mg Midazolam on Day 1 Receives: Drug: Midazolam
Treatment B and C: Inarigivir	Experimental	All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3, Day 6-18 Receives: Drug: Inarigivir
Treatment D: Inarigivir with Midazolam	Experimental	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 Receives: Drug: Midazolam; Drug: Inarigivir

What is being measured

The primary outcome is the main question the study is designed to answer.

Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (Cmax)
Comparison of Cmax for midazolam between Treatments A and D.
Measured: Day 1 Treatment A and Day 19 Treatment D, respectively
Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-t)
Comparison of AUC0-t for midazolam between Treatments A and D.
Measured: Day 1 Treatment A and Day 19 Treatment D, respectively
Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-inf )
Comparison of AUC0-inf for midazolam between Treatments A and D.
Measured: Day 1 Treatment A and Day 19 Treatment D, respectively

Secondary outcomes (3)

Number of Participants With Clinical Relevant Clinical Laboratory, Vital Signs, 12-lead ECG, or Physical Examination
Safety and tolerability were measured via clinical laboratory evaluations, vital signs, 12-lead ECG, or physical examination
Measured: Day -1 to Day 20 and Follow-up (5-9 days post-treatment)
PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (AUC)
A summary of the main plasma PK parameters for inarigivir, Rp-SB 9000, Sp-SB 9000, and Rp-SB 9000 and Sp-SB 9000 combined after a single oral dose of 400 mg inarigivir on Day 3 (Treatment B) and after the last of 14 consecutive daily oral doses of 400 mg inarigivir from Day 6 to 19 (Treatment D)
Measured: Day 3 and Day 6 to 19
PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (Cmax)
A summary of the main plasma PK parameters for inarigivir, Rp-SB 9000, Sp-SB 9000, and Rp-SB 9000 and Sp-SB 9000 combined after a single oral dose of 400 mg inarigivir on Day 3 (Treatment B) and after the last of 14 consecutive daily oral doses of 400 mg inarigivir from Day 6 to 19 (Treatment D)
Measured: Day 3 and Day 6 to 19

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 May 201827 Aug 2018

First posted10 Apr 2018
Study start7 May 2018
Primary completion27 Aug 2018
Study completion27 Aug 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Drug Interaction PotentiationStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03493698
Sponsor's protocol ID: SBP-9200-HBV-202
Other IDs: 2018-000607-16, 2018
Status last verified: Sep 2020
First submitted: 3 Apr 2018
Last updated: 8 Oct 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Open-label, Fixed-Sequence, Drug-Drug Interaction Study Between Multiple Oral Doses of Inarigivir Soproxil and a Single Oral Dose of Midazolam in Healthy Subjects
ClinicalTrials.gov ID: NCT03493698
Acronym / sponsor ID: SBP-9200-HBV-202
Conditions: Drug Interaction Potentiation
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: F-star Therapeutics, Inc.Industry (pharma, biotech, devices)
Collaborators: PRA Health Sciences
Study start: 7 May 2018 (actual)
Primary completion: 27 Aug 2018 (actual)
Study completion: 27 Aug 2018 (actual)
First posted: 10 Apr 2018 (actual)
Results: Posted 8 Oct 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Treatment A: Midazolam	Experimental	Drug: MidazolamAll subjects will receive a single oral dose of 2 mg Midazolam on Day 1
Treatment B and C: Inarigivir	Experimental	Drug: InarigivirAll subjects will receive a single oral dose of 400 mg Inarigivir on Day 3, Day 6-18
Treatment D: Inarigivir with Midazolam	Experimental	Drug: Midazolam, Drug: InarigivirAll 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

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (12 listed)

Gender : male or female
Age : 18-55 years, inclusive, at screening
Body mass index (BMI) : 18.0-30.0 kg/m2, inclusive, at screening
Status : healthy subjects
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

Key exclusion criteria (10 listed)

Employee of PRA or the Sponsor
History of relevant drug and/or food allergies
Using tobacco products within 60 days prior to the first drug administration
History of alcohol abuse or drug addiction (including soft drugs like cannabis products)
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MidazolamMidazolam	Drug	Treatment A: Midazolam, Treatment D: Inarigivir with Midazolam
InarigivirAlso: Inarigivir Soproxil, SB 9200Inarigivir	Drug	Treatment B and C: Inarigivir, Treatment D: Inarigivir with Midazolam

Primary outcome

Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (Cmax)
Time frame: Day 1 Treatment A and Day 19 Treatment D, respectively
Comparison of Cmax for midazolam between Treatments A and D.
Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-t)
Time frame: Day 1 Treatment A and Day 19 Treatment D, respectively
Comparison of AUC0-t for midazolam between Treatments A and D.
Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-inf )
Time frame: Day 1 Treatment A and Day 19 Treatment D, respectively
Comparison of AUC0-inf for midazolam between Treatments A and D.

3 secondary outcomes

Number of Participants With Clinical Relevant Clinical Laboratory, Vital Signs, 12-lead ECG, or Physical Examination
Time frame: Day -1 to Day 20 and Follow-up (5-9 days post-treatment)
PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (AUC)
Time frame: Day 3 and Day 6 to 19
PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (Cmax)
Time frame: Day 3 and Day 6 to 19

Results and safety

Results posted to the registry on 8 Oct 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sequential Single, Multi-day & Combo Midazolam and Inarigivir	17	17

Primary outcome: Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (Cmax)

Time frame: Day 1 Treatment A and Day 19 Treatment D, respectively. Mean (Full Range). Unit: ng/mL

Measure	Treatment A: Midazolam n = 17	Treatment B and C: Inarigivir n = 0	Treatment D: Inarigivir With Midazolam n = 15
Value	12.4 (6.19 to 21.4)	–	13.0 (7.54 to 21.0)

Population analysed: All subjects who received at least one dose of midazolam and had sufficient concentration-time data to reliably estimate PK parameters

Primary outcome: Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-t)

Time frame: Day 1 Treatment A and Day 19 Treatment D, respectively. Mean (Full Range). Unit: h.ng/ml

Measure	Treatment A: Midazolam n = 17	Treatment B and C: Inarigivir n = 0	Treatment D: Inarigivir With Midazolam n = 15
Value	29.9 (16.2 to 57.7)	–	28.7 (15.6 to 44.6)

Population analysed: This outcome measure was prespecified for treatment groups A and D only.

Primary outcome: Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-inf )

Time frame: Day 1 Treatment A and Day 19 Treatment D, respectively. Mean (Full Range). Unit: h.ng/ml

Measure	Treatment A: Midazolam n = 17	Treatment B and C: Inarigivir n = 0	Treatment D: Inarigivir With Midazolam n = 15
Value	31.5 (16.7 to 61.6)	–	30.5 (16.6 to 49.4)

Population analysed: This outcome measure was prespecified for treatment groups A and D only.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 20 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment A: Midazolam	0 of 17 (0%)	4 of 17 (23.5%)	0 of 17
Treatment B: Inarigivir	0 of 17 (0%)	4 of 17 (23.5%)	0 of 17
Treatment C: Inarigivir	0 of 15 (0%)	7 of 17 (41.2%)	0 of 15
Treatment D: Inarigivir With Midazolam	0 of 15 (0%)	2 of 15 (13.3%)	0 of 15

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jeroen van de Wetering principal investigator

PRA Health Sciences

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Midazolam and Inarigivir in people with Drug Interaction Potentiation, run by F-star Therapeutics, Inc. at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (Cmax) (time frame: Day 1 Treatment A and Day 19 Treatment D, respectively). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03493698.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.