Clinical trial NCT05118958: Phase 1 Crossover Study in Healthy Subjects to Evaluate the PK Profile of KVD824 Following Single and Multiple Doses of Modified Release (MR) Formulations
Official title: A Multiple Part, Phase 1 Crossover Study in Healthy Subjects to Evaluate the Pharmacokinetic (PK) Profile of KVD824 Following Single and Multiple Doses of Novel KVD824 Modified Release (MR) Formulations Compared to a Reference KVD824 Immediate Release (IR) Formulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hereditary Angioedema
Lead sponsor: KalVista Pharmaceuticals, Ltd.
Sponsor class: INDUSTRY
First posted: 2021-11-12
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetics - Tlag
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - Tmax
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - Cmax
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - Cmax/Dose
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - C12
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - C24
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - Ctrough
timeFrame: Days 2-14
measure: Pharmacokinetics - Cmin
timeFrame: Days 2-14
measure: Pharmacokinetics - Cavg
timeFrame: Days 2-14
measure: Pharmacokinetics - AUC(0-12)
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - AUC(0-12)/Dose
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - AUC(0-24)
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - AUC(0-24)/Dose
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - AUC(0-last)
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - AUC(0-last)/Dose
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - AUC(0-tau)
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - AUC(0-inf)
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - AUC(0-inf)/D
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - AUCextrap
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - T1/2
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - Lambda-z
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - CL/F
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - CL/Ftau
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - Vz/F
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - Vz/Flau
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - Frel Cmax
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - Frel AUC(0-12)
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - Frel AUC(0-inf)
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - AR Cmax
timeFrame: Days 1, 10 and 14
measure: Pharmacokinetics - Fluctuation
timeFrame: Days 1, 10 and 14
Secondary outcomes:
measure: Safety - Adverse Events
timeFrame: Change from pre-dose to last visit (up to 14 days)
measure: Safety - Serious Adverse Events
timeFrame: Change from pre-dose to last visit (up to 14 days)
measure: Safety - Laboratory Assessments
timeFrame: Throughout the trial to last visit (up to 14 days)
measure: Safety - Vital Signs
timeFrame: Throughout the trial to last visit (up to 14 days)
measure: Safety - ECG
timeFrame: Throughout the trial to last visit (up to 14 days)
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: KalVista Investigative Site
Study officials:
References: