Hereditary AngioedemaPhase 1NCT02448264
First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BCX7353 in Healthy Western and Japanese Volunteers
A Phase 1 study testing BCX7353 in people with Hereditary Angioedema, run by BioCryst Pharmaceuticals at 1 site in United Kingdom.
Trial summary
This is a 3-part Phase 1 dose-ranging study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single (Part 1) and multiple (Part 2) ascending doses of BCX7353 in healthy subjects, and single and multiple doses of BCX7353 in healthy Japanese subjects. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Hereditary Angioedema
- What is being tested?
- BCX7353
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 122 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2015to Dec 2015
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Written informed consent
- Body mass index 19 to 32 kg/m2 and a weight of at least 50 kg
- 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
- Part 3 only: Japanese subjects enrolled in Part 3 must be first generation: born in Japan, not having lived outside Japan > 5 years, able to trace maternal and paternal Japanese ancestry, with no significant change in lifestyle, including diet (at least one Japanese meal consumed per day), since leaving Japan.
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
- Use of over the counter medication within 7 days of dosing and anticipated use through the follow-up visit
- Use of prescription medication within 14 days of dosing and anticipated use through the follow-up visit
- 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.
About this study
Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of BCX7353 in Healthy Subjects
This is a 3-part Phase 1 dose-ranging study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single (Part 1) and multiple (Part 2) ascending doses of BCX7353 in healthy subjects, and single and multiple doses of BCX7353 in healthy Japanese subjects. Pharmacokinetics is an analysis of how the body handles the study drug BCX7353 and pharmacodynamics is an analysis of the activity the study drug BCX7353 may have in the body.
Read the detailed description
Up to 6 ascending, single dose cohorts are planned to be dosed in a sequential manner in Part 1 of the study. Eight subjects will be treated with a single dose of study drug per dose cohort (6 subjects per cohort will receive BCX7353 and 2 subjects per cohort will receive matching placebo). Escalation to the next higher dose level will occur only after completion of a review of clinical safety and pharmacokinetics by the Sponsor and PI.
Up to 4 ascending, multiple dose cohorts will be enrolled in a sequential manner in Part 2 of the study. Twelve subjects will be treated with study drug per dose cohort (10 subjects will receive BCX7353 and 2 subjects will receive placebo per cohort). The planned doses, dosing regimens, and duration of dosing (7 or 14 days) for each of the Part 2 cohorts will be determined based upon safety and pharmacokinetic data collected during the study. Escalation to the next higher dose level in Part 2 will occur only after completion of a review of clinical safety and pharmacokinetics by the Sponsor and clinical site study physician.
In Part 3 of the study, the safety, tolerability, PK, and PD of single and multiple doses of oral BCX7353 versus placebo in healthy subjects of Japanese origin will be evaluated. In the single dose cohort, 16 Japanese subjects will be randomized into a single cohort to receive either placebo or 1 of 2 active doses of BCX7353. In the multiple dose cohort, twelve subjects will be treated with study drug (10 subjects will receive BCX7353 and 2 subjects will receive placebo per cohort). The planned doses (single and multiple dose cohort), and dosing regimen and duration of dosing (7 or 14 days; multple dose cohort) for Part 3 will be determined based upon safety and pharmacokinetic data collected during Parts 1 and 2 of the study.
- Conditions
- Hereditary Angioedema
- Being tested
- BCX7353, Placebo to match BCX7353
- Keywords
- kallikrein inhibitor, oral prophylaxis, BioCryst, first-in-human, hereditary angioedema
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCX7353Drug
Placebo to match BCX7353Drug
| Study group | Role | What they receive |
|---|---|---|
| BCX7353 | Experimental | BCX7353 capsules administered orally Receives: Drug: BCX7353 |
| Placebo | Placebo comparator | Placebo to Match BCX7353 capsules, administered orally Receives: Drug: Placebo to match BCX7353 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Measured: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration)
Laboratory analyses
Measured: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration)
Vital signs
Measured: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration)
Electrocardiograms
Measured: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration)
Physical examination findings
Measured: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration)
Secondary outcomes (11)
Plasma BCX7353 Cmax
Measured: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 Tmax
Measured: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 average steady-state concentration
Measured: steady-state plasma pharmacokinetic parameters are based on blood sampling through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 AUCinf
Measured: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort
Plasma BCX7353 AUCtau
Measured: steady-state plasma pharmacokinetic parameters are based on blood sampling through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 AUC0-t
Measured: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 t1/2
Measured: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 apparent oral clearance
Measured: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 apparent volume of distribution
Measured: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 accumulation ratio
Measured: steady-state plasma pharmacokinetic parameters are based on blood sampling through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma pharmacodynamics of BCX7353
Outcome evaluated by change from baseline in ex vivo kallikrein inhibition
Measured: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2015 (estimated)
- Study startMay 2015
- Primary completionNov 2015
- Study completionDec 2015
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioCryst Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Joanne Collier, MBChB, FFPM, Dip Stats (OU), Principal investigator, Quotient Clinical Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02448264
- Sponsor's protocol ID
- BCX7353-101
- Status last verified
- Jan 2016
- First submitted
- 13 May 2015
- Last updated
- 13 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of BCX7353 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02448264
- Acronym / sponsor ID
- BCX7353-101
- Conditions
- Hereditary Angioedema
- Keywords
- kallikrein inhibitor, oral prophylaxis, BioCryst, first-in-human, hereditary angioedema
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- BioCryst PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- May 2015
- Primary completion
- Nov 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 19 May 2015 (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 a 3-part Phase 1 dose-ranging study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single (Part 1) and multiple (Part 2) ascending doses of BCX7353 in healthy subjects, and single and multiple doses of BCX7353 in healthy Japanese subjects. Pharmacokinetics is an analysis of how the body handles the study drug BCX7353 and pharmacodynamics is an analysis of the activity the study drug BCX7353 may have in the body.
Detailed description
Up to 6 ascending, single dose cohorts are planned to be dosed in a sequential manner in Part 1 of the study. Eight subjects will be treated with a single dose of study drug per dose cohort (6 subjects per cohort will receive BCX7353 and 2 subjects per cohort will receive matching placebo). Escalation to the next higher dose level will occur only after completion of a review of clinical safety and pharmacokinetics by the Sponsor and PI.
Up to 4 ascending, multiple dose cohorts will be enrolled in a sequential manner in Part 2 of the study. Twelve subjects will be treated with study drug per dose cohort (10 subjects will receive BCX7353 and 2 subjects will receive placebo per cohort). The planned doses, dosing regimens, and duration of dosing (7 or 14 days) for each of the Part 2 cohorts will be determined based upon safety and pharmacokinetic data collected during the study. Escalation to the next higher dose level in Part 2 will occur only after completion of a review of clinical safety and pharmacokinetics by the Sponsor and clinical site study physician.
In Part 3 of the study, the safety, tolerability, PK, and PD of single and multiple doses of oral BCX7353 versus placebo in healthy subjects of Japanese origin will be evaluated. In the single dose cohort, 16 Japanese subjects will be randomized into a single cohort to receive either placebo or 1 of 2 active doses of BCX7353. In the multiple dose cohort, twelve subjects will be treated with study drug (10 subjects will receive BCX7353 and 2 subjects will receive placebo per cohort). The planned doses (single and multiple dose cohort), and dosing regimen and duration of dosing (7 or 14 days; multple dose cohort) for Part 3 will be determined based upon safety and pharmacokinetic data collected during Parts 1 and 2 of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BCX7353 | Experimental | Drug: BCX7353BCX7353 capsules administered orally |
| Placebo | Placebo comparator | Drug: Placebo to match BCX7353Placebo to Match BCX7353 capsules, administered orally |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Written informed consent
- Body mass index 19 to 32 kg/m2 and a weight of at least 50 kg
- 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
- Use of over the counter medication within 7 days of dosing and anticipated use through the follow-up visit
- Use of prescription medication within 14 days of dosing and anticipated use through the follow-up visit
- 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 | Drug | BCX7353 |
| Placebo to match BCX7353 | Drug | Placebo |
Primary outcome
Adverse events
Time frame: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration)
Laboratory analyses
Time frame: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration)
Vital signs
Time frame: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration)
Electrocardiograms
Time frame: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration)
Physical examination findings
Time frame: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration)
11 secondary outcomes
Plasma BCX7353 Cmax
Time frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 Tmax
Time frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 average steady-state concentration
Time frame: steady-state plasma pharmacokinetic parameters are based on blood sampling through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 AUCinf
Time frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort
Plasma BCX7353 AUCtau
Time frame: steady-state plasma pharmacokinetic parameters are based on blood sampling through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 AUC0-t
Time frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 t1/2
Time frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 apparent oral clearance
Time frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 apparent volume of distribution
Time frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma BCX7353 accumulation ratio
Time frame: steady-state plasma pharmacokinetic parameters are based on blood sampling through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
Plasma pharmacodynamics of BCX7353
Time frame: plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort and through Day 14 or 21 for Part 2 and Part 3 multiple dose cohort (Day depends on dosing duration)
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 13 Jan 2016.
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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.
Joanne Collier, MBChB, FFPM, Dip Stats (OU) 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 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 6 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 13 Jan 2016. 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. Some participants in this study may receive a placebo. 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?
Adverse events (time frame: Part 1 and Part 3 single dose cohort: absolute and change from baseline through Study Day 7; Part 2 and Part 3 multiple dose cohort: absolute and change from baseline through 14 or 21 days (depending on dosing duration)). The study lists 5 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 13 Jan 2016.