Phase 1 Crossover Study in Healthy Subjects to Evaluate the PK Profile of KVD824 Following Single and Multiple Doses of Modified Release (MR) Formulations
Hereditary Angioedema
About this trial
This is an interventional treatment trial for Hereditary Angioedema
Eligibility Criteria
Inclusion Criteria:
- Healthy males or non-pregnant, non-lactating healthy females.
- Aged 18 to 55 years, inclusive at the time of signing informed consent.
- Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening.
- Must be willing and able to communicate and participate in the whole study.
- Must provide written informed consent.
- Must agree to adhere to the contraception requirements.
Exclusion Criteria:
- Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1.
- Subjects who are study site employees, sponsor employees, or immediate family members of site or sponsor employees.
- Subjects who have previously been administered IMP in this study. Subjects who have taken part in one part of this study are not permitted to take part in any other study part.
- History of any drug or alcohol abuse in the past 2 years.
- Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type).
- A confirmed positive alcohol breath test at screening or admission.
- Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission.
- Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months.
- Females of childbearing potential who are pregnant or lactating (all female subjects must have a negative serum pregnancy test at screening and urine pregnancy test on admission).
- Subjects with pregnant or lactating partners.
- Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening.
- Clinically significant abnormal clinical chemistry, haematology, coagulation or urinalysis as judged by the investigator. Subjects with Gilbert's Syndrome are allowed.
- Confirmed positive drugs of abuse test result.
- Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results.
- Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <70 mL/min using the Cockcroft-Gault equation.
- History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator.
- Subjects with a history of cholecystectomy or gall stones.
- Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
- Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.
- Donation or loss of greater than 400 mL of blood within the previous 3 months.
- Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than up to 4 g of paracetamol per day, HRT or hormonal contraception) in the 14 days before IMP administration.
- Failure to satisfy the investigator of fitness to participate for any other reason.
Sites / Locations
- KalVista Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Active Comparator
Part 1 - Period 1 - Prototype 1 600 mg (single dose fasted)
Part 1 - Period 3 - Prototype 2 600 mg (single dose fasted)
Part 1 - Period 4 - Prototype 1 900 mg (single dose fasted)
Part 1 - Period 5 - Prototype 1 600 mg and Prototype 3 300 mg (single dose fasted)
Part 1 - Period 6 - Prototype 1 900 mg (single dose fed)
Part 3 - KVD824 Prototype 1 600 mg (multiple dose fed)
Part 3 - Placebo to KVD824 Prototype 1 600 mg (multiple dose fed)
Part 3 - KVD824 Prototype 1 900 mg (multiple dose fed)
Part 3 - Placebo to KVD824 Prototype 1 900 mg (multiple dose fed)
Part 3 - KVD824 Prototype 1 900 mg (multiple dose fasted)
Part 3 - Placebo to KVD824 Prototype 1 900 mg (multiple dose fasted)
Part 1 - Period 2 - KVD824 IR Capsule 600 mg (single dose fasted)
600 mg (2 x 300 mg) KVD824 prototype 1 modified-release tablet dosed orally in fasted state as a single dose
600 mg (2 x 300 mg) KVD824 prototype 2 modified-release tablet dosed orally in fasted state as a single dose
900 mg (3 x 300 mg) KVD824 prototype 1 modified-release tablet dosed orally in fasted state as a single dose
600 mg (2 x 300 mg) KVD824 prototype 1 modified-release tablet plus 300 mg (1 x 300 mg) Prototype 3 dosed orally in fasted state as a single dose
900 mg (3 x 300 mg) KVD824 prototype 1 modified-release tablet dosed orally in fed state as a single dose
600 mg (2 x 300 mg) KVD824 prototype 1 modified-release tablet dosed orally twice daily in fed state for 13 days with a single dose on day 14.
Placebo to 600 mg KVD824 prototype 1 modified-release tablet dosed orally twice daily in fed state for 13 days with a single dose on day 14.
900 mg (3 x 300 mg) KVD824 prototype 1 modified-release tablet dosed orally twice daily in fed state for 13 days with a single dose on day 14.
Placebo to 900 mg KVD824 prototype 1 modified-release tablet dosed orally twice daily in fed state for 13 days with a single dose on day 14.
900 mg (3 x 300 mg) KVD824 prototype 1 modified-release tablet dosed orally twice daily in fasted state for 13 days with a single dose on day 14.
Placebo to 900 mg KVD824 prototype 1 modified-release tablet dosed orally twice daily in fasted state for 13 days with a single dose on day 14.
600 mg (2 x 300 mg) KVD824 immediate release Capsule dosed orally in fasted state as a single dose