Phase 1 Crossover Study in Healthy Subjects to Evaluate the PK Profile of KVD824 Following Single and Multiple Doses of Modified Release (MR) Formulations

KalVista Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Hereditary Angioedema

Treatments: Drug: Placebo to KVD824 Prototype 1; Drug: KVD824 Prototype 2 modified-release tablet; Drug: KVD824 Prototype 1 modified-release tablet; Drug: KVD824 Immediate-Release Capsule; Drug: KVD824 Prototype 3 modified-release tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT05118958

KVD824-102

Details and patient eligibility

About

This is a 3 part, phase 1 crossover study in healthy subjects to evaluate the pharmacokinetic profile of KVD824 following single and multiple doses of novel KVD824 modified-release formulations compared with a reference KVD824 immediate release formulation.

Full description

Part 1 of the study was a single-centre, open-label, non-randomised, 6-period crossover study designed to investigate the PK and safety of KVD824 MR prototype formulations (with or without an additional KVD824 IR capsule) compared to a reference KVD824 IR capsule formulation in healthy male and female subjects. Part 2 was an optional part designed to investigate the PK and safety of a selected KVD824 MR prototype tablet formulation (with or without an additional KVD824 IR capsule) in healthy male and female subjects in both the fed and fasted state. Note: this Part was not conducted as sufficient information on food effect was collected in the other Parts of the study.

Part 3 was a single-centre, randomised, double-blind, placebo-controlled, multiple dose group study to investigate the PK and safety of a selected KVD824 MR prototype tablet formulation (with or without an additional KVD824 IR capsule) in healthy male and female subjects. Part 3 started following completion of Part 1.

Enrollment: 37 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy males or non-pregnant, non-lactating healthy females.
2. Aged 18 to 55 years, inclusive at the time of signing informed consent.
3. Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening.
4. Must be willing and able to communicate and participate in the whole study.
5. Must provide written informed consent.
6. Must agree to adhere to the contraception requirements.

Exclusion criteria

1. Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1.
2. Subjects who are study site employees, sponsor employees, or immediate family members of site or sponsor employees.
3. 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.
4. History of any drug or alcohol abuse in the past 2 years.
5. 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).
6. A confirmed positive alcohol breath test at screening or admission.
7. 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.
8. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months.
9. 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).
10. Subjects with pregnant or lactating partners.
11. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening.
12. Clinically significant abnormal clinical chemistry, haematology, coagulation or urinalysis as judged by the investigator. Subjects with Gilbert's Syndrome are allowed.
13. Confirmed positive drugs of abuse test result.
14. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results.
15. Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <70 mL/min using the Cockcroft-Gault equation.
16. History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator.
17. Subjects with a history of cholecystectomy or gall stones.
18. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
19. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.
20. Donation or loss of greater than 400 mL of blood within the previous 3 months.
21. 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.
22. Failure to satisfy the investigator of fitness to participate for any other reason.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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37 participants in 12 patient groups, including a placebo group

Part 1 - Period 1 - Prototype 1 600 mg (single dose fasted)

Experimental group

Description:

600 mg (2 x 300 mg) KVD824 prototype 1 modified-release tablet dosed orally in fasted state as a single dose

Treatment:

Drug: KVD824 Prototype 1 modified-release tablet

Part 1 - Period 3 - Prototype 2 600 mg (single dose fasted)

Experimental group

Description:

600 mg (2 x 300 mg) KVD824 prototype 2 modified-release tablet dosed orally in fasted state as a single dose

Treatment:

Drug: KVD824 Prototype 2 modified-release tablet

Part 1 - Period 4 - Prototype 1 900 mg (single dose fasted)

Experimental group

Description:

900 mg (3 x 300 mg) KVD824 prototype 1 modified-release tablet dosed orally in fasted state as a single dose

Treatment:

Drug: KVD824 Prototype 1 modified-release tablet

Part 1 - Period 5 - Prototype 1 600 mg and Prototype 3 300 mg (single dose fasted)

Experimental group

Description:

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

Treatment:

Drug: KVD824 Prototype 3 modified-release tablet

Drug: KVD824 Prototype 1 modified-release tablet

Part 1 - Period 6 - Prototype 1 900 mg (single dose fed)

Experimental group

Description:

900 mg (3 x 300 mg) KVD824 prototype 1 modified-release tablet dosed orally in fed state as a single dose

Treatment:

Drug: KVD824 Prototype 1 modified-release tablet

Part 3 - KVD824 Prototype 1 600 mg (multiple dose fed)

Experimental group

Description:

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.

Treatment:

Drug: KVD824 Prototype 1 modified-release tablet

Part 3 - Placebo to KVD824 Prototype 1 600 mg (multiple dose fed)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo to KVD824 Prototype 1

Part 3 - KVD824 Prototype 1 900 mg (multiple dose fed)

Experimental group

Description:

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.

Treatment:

Drug: KVD824 Prototype 1 modified-release tablet

Part 3 - Placebo to KVD824 Prototype 1 900 mg (multiple dose fed)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo to KVD824 Prototype 1

Part 3 - KVD824 Prototype 1 900 mg (multiple dose fasted)

Experimental group

Description:

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.

Treatment:

Drug: KVD824 Prototype 1 modified-release tablet

Part 3 - Placebo to KVD824 Prototype 1 900 mg (multiple dose fasted)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo to KVD824 Prototype 1

Part 1 - Period 2 - KVD824 IR Capsule 600 mg (single dose fasted)

Active Comparator group

Description:

600 mg (2 x 300 mg) KVD824 immediate release Capsule dosed orally in fasted state as a single dose

Treatment:

Drug: KVD824 Immediate-Release Capsule