Hereditary AngioedemaPhase 1NCT02819102
An Open-label Drug-Drug Interaction Study to Evaluate the Effect of BCX7353 on Cytochrome P450 Enzyme Activity Using Probe Substrates
A Phase 1 study testing BCX7353 and probes in people with Hereditary Angioedema, run by BioCryst Pharmaceuticals at 1 site in United Kingdom.
Trial summary
This is an open-label, single sequence study to evaluate the effect of BCX7353 on hepatic and intestinal cytochrome P450 enzymes using probe substrate drugs in healthy subjects. Pharmacokinetics of the probe substrate drugs will be measured prior to and following administration of multiple doses of BCX7353. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Hereditary Angioedema
- What is being tested?
- BCX7353 and probes
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 2016to Jun 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Written informed consent
- Body mass index 18 to 32 kg/m2
- Abides by study restrictions
- Attends all study visits and agrees to remain in study center for the confinement period
- Acceptable birth control measures for male subjects and women of childbearing potential
Who cannot join
- Clinically significant medical history, current medical or psychiatric condition. This includes a history of clinically significant gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, neurological, or cardiac disease
- Clinically significant ECG finding, vital sign measurement or laboratory/urinalysis abnormality at screening or baseline
- Poor or ultra- metabolizers of CYP2C19 or CYP2D6 Use of over the counter or prescription medication within 14 days of dosing and anticipated use through the follow-up visit
- Use of medication or consumption of any substance that is known to inhibit or induce metabolic enzymes or transporters within 30 days of dosing
- Participation in any other investigational drug study within 90 days of screening
- Recent or current history of alcohol or drug abuse
Show all 11Show fewer
- Regular recent use of tobacco or nicotine products
- Positive serology for HBV, HCV, or HIV
- Pregnant or nursing
- Donation or loss of greater than 400 mL of blood within 3 months
- Serious adverse reaction or serious hypersensitivity to any drug
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Quotient Clinical Ltd
Ruddington, Nottingham, NG11 6JS
About this study
Official title: A Single Sequence, Open-Label Drug-Drug Interaction Study to Evaluate the Effect of BCX7353 on Cytochrome P450 3A4, 2C9, 2C19 and 2D6 Enzyme Activity Using Probe Substrates in Healthy Subjects
This is an open-label, single sequence study to evaluate the effect of BCX7353 on hepatic and intestinal cytochrome P450 enzymes using probe substrate drugs in healthy subjects. Pharmacokinetics of the probe substrate drugs will be measured prior to and following administration of multiple doses of BCX7353.
Read the detailed description
This is a single centre, single sequence, open-label, study to evaluate the effect of BCX7353 on hepatic and intestinal cytochrome P450 (CYP) 3A4 (midazolam IV and PO, respectively), CYP2C9 (tolbutamide), CYP2C19 (omeprazole) and CYP2D6 (dextromethorphan) enzyme activity using probe substrate drugs in healthy subjects. Pharmacokinetics of the probe substrate drugs will be measured prior to and following administration of multiple doses of BCX7353.
Twenty healthy male and female subjects are planned for dosing.
Each subject will receive the following treatments:
Day 1: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, and 30 mg dextromethorphan orally.
Day 2: a single oral dose of 2 mg midazolam. Days 3 to 9: 350 mg BCX7353 once a day. Day 10: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, 30 mg dextromethorphan and 350 mg BCX7353, orally.
Day 11: a single oral dose of 2 mg of midazolam along with 350 mg BCX7353.
- Conditions
- Hereditary Angioedema
- Being tested
- BCX7353 and probes
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCX7353 and probesDrug
| Study group | Role | What they receive |
|---|---|---|
| Metabolic Probes and BCX7353 | Experimental | Day 1: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, and 30 mg dextromethorphan orally.
Day 2: a single oral dose of 2 mg midazolam. Days 3 to 9: 350 mg BCX7353 once a day. Day 10: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, 30 mg dextromethorphan and 350 mg BCX7353, orally.
Day 11: a single oral dose of 2 mg of midazolam along with 350 mg BCX7353. Receives: Drug: BCX7353 and probes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax of probe substrates
Measured: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Tmax of probe substrates
Measured: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
AUClast of probe substrates
Measured: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
AUCinf of probe substrates
Measured: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
t1/2 of probe substrates
Measured: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Cl of intravenous midazolam
Measured: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Secondary outcomes (12)
adverse events
Measured: absolute and change from baseline through study day 11
laboratory analyses
Measured: absolute and change from baseline through study day 11
Vital signs
Measured: absolute and change from baseline through study day 11
physical examination findings
Measured: absolute and change from baseline through study day 11
electrocardiograms
Measured: absolute and change from baseline through study day 11
C24 for tolbutamide
Measured: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
C6 for IV and oral midazolam
Measured: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Probe/metabolite AUC24 ratio
Measured: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Tlag of probe substrates
Measured: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
VdF of probe substrates
Measured: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
CL/F of oral probe substrates
Measured: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Vss of intravenous midazolam
Measured: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2016 (estimated)
- Study startMar 2016
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary AngioedemaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BioCryst Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Litza McKenzie, MBChB, Principal investigator, Quotient Clinical Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02819102
- Sponsor's protocol ID
- BCX7353-102
- Status last verified
- Jun 2016
- First submitted
- 28 Jun 2016
- Last updated
- 31 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Sequence, Open-Label Drug-Drug Interaction Study to Evaluate the Effect of BCX7353 on Cytochrome P450 3A4, 2C9, 2C19 and 2D6 Enzyme Activity Using Probe Substrates in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02819102
- Acronym / sponsor ID
- BCX7353-102
- Conditions
- Hereditary Angioedema
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- BioCryst PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Mar 2016
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 30 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, single sequence study to evaluate the effect of BCX7353 on hepatic and intestinal cytochrome P450 enzymes using probe substrate drugs in healthy subjects. Pharmacokinetics of the probe substrate drugs will be measured prior to and following administration of multiple doses of BCX7353.
Detailed description
This is a single centre, single sequence, open-label, study to evaluate the effect of BCX7353 on hepatic and intestinal cytochrome P450 (CYP) 3A4 (midazolam IV and PO, respectively), CYP2C9 (tolbutamide), CYP2C19 (omeprazole) and CYP2D6 (dextromethorphan) enzyme activity using probe substrate drugs in healthy subjects. Pharmacokinetics of the probe substrate drugs will be measured prior to and following administration of multiple doses of BCX7353.
Twenty healthy male and female subjects are planned for dosing.
Each subject will receive the following treatments:
Day 1: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, and 30 mg dextromethorphan orally.
Day 2: a single oral dose of 2 mg midazolam. Days 3 to 9: 350 mg BCX7353 once a day. Day 10: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, 30 mg dextromethorphan and 350 mg BCX7353, orally.
Day 11: a single oral dose of 2 mg of midazolam along with 350 mg BCX7353.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metabolic Probes and BCX7353 | Experimental | Drug: BCX7353 and probesDay 1: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, and 30 mg dextromethorphan orally. Day 2: a single oral dose of 2 mg midazolam. Days 3 to 9: 350 mg BCX7353 once a day. Day 10: 1 mg midazolam will be administered as an IV bolus simultaneously to administration of 500 mg tolbutamide, 40 mg omeprazole, 30 mg dextromethorphan and 350 mg BCX7353, orally. Day 11: a single oral dose of 2 mg of midazolam along with 350 mg BCX7353. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Written informed consent
- Body mass index 18 to 32 kg/m2
- Abides by study restrictions
- Attends all study visits and agrees to remain in study center for the confinement period
- Acceptable birth control measures for male subjects and women of childbearing potential
Key exclusion criteria (11 listed)
- Clinically significant medical history, current medical or psychiatric condition. This includes a history of clinically significant gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, neurological, or cardiac disease
- Clinically significant ECG finding, vital sign measurement or laboratory/urinalysis abnormality at screening or baseline
- Poor or ultra- metabolizers of CYP2C19 or CYP2D6 Use of over the counter or prescription medication within 14 days of dosing and anticipated use through the follow-up visit
- Use of medication or consumption of any substance that is known to inhibit or induce metabolic enzymes or transporters within 30 days of dosing
- Participation in any other investigational drug study within 90 days of screening
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 |
|---|---|---|
| BCX7353 and probes | Drug | Metabolic Probes and BCX7353 |
Primary outcome
Cmax of probe substrates
Time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Tmax of probe substrates
Time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
AUClast of probe substrates
Time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
AUCinf of probe substrates
Time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
t1/2 of probe substrates
Time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Cl of intravenous midazolam
Time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
12 secondary outcomes
adverse events
Time frame: absolute and change from baseline through study day 11
laboratory analyses
Time frame: absolute and change from baseline through study day 11
Vital signs
Time frame: absolute and change from baseline through study day 11
physical examination findings
Time frame: absolute and change from baseline through study day 11
electrocardiograms
Time frame: absolute and change from baseline through study day 11
C24 for tolbutamide
Time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
C6 for IV and oral midazolam
Time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Probe/metabolite AUC24 ratio
Time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Tlag of probe substrates
Time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
VdF of probe substrates
Time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
CL/F of oral probe substrates
Time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Vss of intravenous midazolam
Time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2017.
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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.
Litza McKenzie, MBChB principal investigator
Quotient Clinical Ltd
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 BCX7353 and probes in people with Hereditary Angioedema, run by BioCryst Pharmaceuticals at 1 site in United Kingdom.
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 5 inclusion and 11 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 31 Jan 2017. 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 United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Cmax of probe substrates (time frame: plasma pharmacokinetic parameters are based on blood sampling through 24 hours on Day 1, 2, 10 and 11). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Jan 2017.