Clinical trial NCT04349800: A Single Dose Safety, Tolerability, Pharmacokinetic and Food Effect Study of KVD900 (Sebetralstat) in Healthy Volunteers
Official title: A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of KVD900 Followed by Crossover Sub-studies of KVD900 Formulations, and Food Effect in Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hereditary Angioedema
Keywords: Sebetralstat
Lead sponsor: KalVista Pharmaceuticals, Ltd.
Sponsor class: INDUSTRY
First posted: 2020-04-16
Enrollment: 84
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A safety, tolerability, pharmacokinetic and food effect study of KVD900 in healthy volunteers.


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects between 18 and 55 years of age.
* Healthy subjects as determined by past medical history and as judged by the Chief Investigator or designee.
* Male subject willing to use a highly effective method of contraception.
* Subject with a body mass index (BMI) of 18-32 kg/m2.
* Subject with no clinically significant history of previous allergy or sensitivity to KVD900 or any of the excipients contained within the investigational medicinal product (IMP).
* Subject with no clinically significant abnormal serum biochemistry, haematology, clotting profiles, and urine examination values within 28 days before the first dose of IMP.
* Subject with a negative urinary drugs of abuse screen, determined within 28 days before the first dose of IMP
* Subject with negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results.
* Subject with no clinically significant abnormalities in 12-lead electrocardiogram
* Subjects must not donate sperm from first dose until at least 3 months after last dose of IMP.
* Subjects without any special food restrictions that would hinder ability to consume the high fat breakfast provided during study Part C; such as lactose intolerance , vegan, low-fat, low sodium, etc.
* Subjects with no known allergy or sensitivity to lactose and/or any additional excipients contained in IMP.
* Subject must be available to complete the study (including all follow up visits).
* Subject must satisfy the Chief Investigator or designee about their fitness to participate in the study.
* Subject must provide written informed consent to participate in the study.

Exclusion Criteria:

* A clinically significant history of gastrointestinal disorder likely to influence IMP absorption.
* Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements .
* Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular (no history of syncope or vasovagal events), or metabolic dysfunction.
* Subjects with a history of clotting abnormalities.
* A clinically significant history of drug or alcohol abuse in the last 5 years.
* Users of nicotine products i.e., current smokers or ex-smokers who have smoked within the 6 months prior to dosing with the study medication or users of cigarette replacements.
* Inability to communicate well with Investigators.
* Participation in a New Chemical Entity clinical study within the previous 3 months or a marketed drug clinical study within the 30 days before the first dose of IMP.
* Donation of 450 mL or more blood within the 3 months before the first dose of IMP.

Primary outcomes:
measure: Number of Subjects with Adverse Events
timeFrame: Change from pre-dose to last visit, 5-7 days post dose.
measure: Number of Subjects with Serious Adverse Events
timeFrame: Change from pre-dose to last visit, 5-7 days post dose.
measure: Number of participants with clinically significant changes in laboratory assessments
timeFrame: Throughout study until last visit, 5-7 days post dose.
measure: Number of participants with clinically significant changes in vital signs
timeFrame: Throughout study until last visit, 5-7 days post dose.
measure: Number of participants with clinically significant changes in electrocardiogram (ECG) measurements
timeFrame: Throughout study until last visit, 5-7 days post dose.
Secondary outcomes:
measure: Pharmacokinetics - Cmax
timeFrame: Up to 48 hours post dose
measure: Pharmacokinetics - AUC0-t
timeFrame: Up to 48 hours post dose
measure: Pharmacokinetics - AUC0-24
timeFrame: Up to 24 hours post dose
measure: Pharmacokinetics - AUC0-inf
timeFrame: Up to 48 hours post dose
measure: Pharmacokinetics - food effect (Part C only)
timeFrame: Up to 24 hours post dose
measure: Pharmacokinetics - formulation bridge - relative bioavailability (Part B only)
timeFrame: Up to 24 hours post dose
Other outcomes:
Locations:
city: Wales
country: United Kingdom
facility: KalVista Investigative Site
Study officials:
References:
citation: Maetzel A, Smith MD, Duckworth EJ, Hampton SL, De Donatis GM, Murugesan N, Rushbrooke LJ, Li L, Francombe D, Feener EP, Yea CM. KVD900, an oral on-demand treatment for hereditary angioedema: Phase 1 study results. J Allergy Clin Immunol. 2022 Jun;149(6):2034-2042. doi: 10.1016/j.jaci.2021.10.038. Epub 2022 Jan 24.