First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BCX7353 in Healthy Western and Japanese Volunteers

NCT02448264 | Completed Phase 1

• 1 other identifier: BCX7353-101
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Hereditary Angioedema

Keywords

kallikrein inhibitor; oral prophylaxis; BioCryst; first-in-human; hereditary angioedema

Outcome Measures

Primary Outcomes (5)

• Adverse events

  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

  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

  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

  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

  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

  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

  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

  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

  plasma pharmacokinetic parameters are based on blood sampling through Day 5 for Part 1 and Part 3 single dose cohort

• Plasma BCX7353 AUCtau

  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)

Study Arms (2)

BCX7353

EXPERIMENTAL

BCX7353 capsules administered orally

Drug: BCX7353

Placebo

PLACEBO COMPARATOR

Placebo to Match BCX7353 capsules, administered orally

Drug: Placebo to match BCX7353

Interventions

BCX7353 DRUG

BCX7353

Placebo to match BCX7353 DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• BioCryst Pharmaceuticals: lead

Study Sites (1)

Quotient Clinical

Ruddington, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

berotralstat

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Study Officials

• Joanne Collier, MBChB, FFPM, Dip Stats (OU)

  Quotient Clinical Ltd

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2015
• First Posted: May 19, 2015
• Study Start: May 1, 2015
• Primary Completion: November 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 13, 2016

Record last verified: 2016-01

Locations

GB (1)