Hereditary angioedema Genetic Diseases
Conditions
Interventions
Each participant receives single oral doses of different KVD824 gastro-retentive (GR) prototype tablet formulations (which may be radiolabelled) in a fed or fasted state, and a reference KVD824 modifi
Sponsors
KalVista Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must provide written informed consent 2. Must be willing and able to communicate and participate in the whole trial part 3. Aged 30 to 55 years inclusive for Part 1 and 18 to 55 years inclusive for Parts 2 and 3 at the time of signing informed consent 4. Must agree to adhere to the contraception requirements defined in the Clinical Protocol 5. Healthy males or non-pregnant, non-lactating healthy females. In Part 1, females must be of non-childbearing potential 6. Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening 7. Willing to consume a high-fat meal, including pork (high-fat food-effect regimens only)
Exclusion criteria
Exclusion criteria: 1. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients 2. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active 3. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease (in Part 1, especially peptic ulceration, GI bleeding, ulcerative colitis, Crohn’s Disease or irritable bowel syndrome), neurological or psychiatric disorder, as judged by the investigator 4. Volunteers with a history of cholecystectomy or gallstones (high-fat food-effect regimens only) 5. History of GI surgery (with the exception of appendectomy unless it was performed within the previous 12 months) 6. Part 1 only: Presence of non-removable metal objects such as metal plates, screws, etc, in the abdominal region of the body. Very small metal items (e.g. sterilisation clips, hernia repair staples) are permitted 7. Part 1 only: Acute diarrhoea or constipation in the 7 days before the predicted Day 1. If screening occurs >7 days before Day 1, this criterion will be determined on Day 1. Diarrhoea will be defined as the passage of liquid faeces and/or a stool frequency of greater than 3 times per day. Constipation will be defined as a failure to open the bowels more frequently than every other day 8. Volunteers who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening 9. Evidence of current SARS-CoV-2 infection 10. Clinically significant abnormal clinical chemistry, haematology, coagulation or urinalysis as judged by the investigator. Volunteers with Gilbert’s Syndrome are allowed. 11. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results 12. Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <70 mL/min using the Cockcroft-Gault equation 13. Females who are pregnant or lactating (all female volunteers must have a negative serum pregnancy test at screening and a negative highly sensitive urine pregnancy test at each admission) 14. Volunteers who have received any IMP in a clinical research trial within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer 15. Volunteers who have previously been administered IMP in this trial. Volunteers who have taken part in one part of the trial are not permitted to take part in another part of the trial 16. Volunteers who report to have previously received KVD824 17. Part 1 only: radiation exposure, including that from the present trial, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the trial 18. Part 1 only: volunteers who have been administered IMP in an ADME trial in the last 6 months 19. Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood 20. Volunteers 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. COVID-19 vaccines are accepted concomitant medicat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Measurement of the following PK parameters in plasma: Tlag, Tmax, Cmax, C12, C24, AUC(0-12), AUC(0-24), AUC(0-last), AUC(0-inf), T1/2 and Frels (as appropriate) at multiple timepoints up to 48 hours post-dose (Part 1) 2. A comparison of the in vivo transit and radiolabel release from KVD824 GR prototype tablet formulations by measuring the following scintigraphic parameters: last time in stomach, gastric emptying (GE), small bowel transit, colon arrival (CA), time and location of initial radiolabel release (IRR) and complete radiolabel release (CRR) up to 24 hours post dose (Part 1) 3. Measurement of the following PK parameters in plasma: Tlag, Tmax, Cmax, C12, C24, AUC(0-12), AUC(0-24), AUC(0-last), AUC(0-inf), T1/2 and Frels (as appropriate) at multiple timepoints up to 48 hours post-dose (Part 2 – optional) 4. Measurement of the following PK parameters in plasma: Tmax, Cmax, C12, C24, AUC(0-tau) and T1/2 on Days 1 and 7, and Day 6 evening dose, as appropriate, at multiple timepoints up to 48 hours post-final dose and pre-dose concentrations on each dosing day following multiple dosing (Part 3) | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of adverse events and assessment of safety laboratory tests, vital signs, electrocardiograms and physical examinations from the time of signing the informed consent form up until discharge from the study | — |
Countries
England, United Kingdom
Contacts
Public ContactClinical Studies Information
Outcome results
None listed