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

Primary Purpose

Hereditary Angioedema

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
KVD824 Prototype 1 modified-release tablet
KVD824 Prototype 2 modified-release tablet
KVD824 Immediate-Release Capsule
Placebo to KVD824 Prototype 1
KVD824 Prototype 3 modified-release tablet
Sponsored by
KalVista Pharmaceuticals, Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hereditary Angioedema

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts 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.

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

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Active Comparator

Arm Label

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)

Arm Description

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

Outcomes

Primary Outcome Measures

Pharmacokinetics - Tlag
Time prior to the first measurable concentration after single and multiple doses of KVD824
Pharmacokinetics - Tmax
Time of maximum observed concentration after single and multiple doses of KVD824 with and without food
Pharmacokinetics - Cmax
Maximum observed concentration after single and multiple doses of KVD824 with and without food
Pharmacokinetics - Cmax/Dose
Maximum observed concentration divided by dose
Pharmacokinetics - C12
Plasma concentration observed at time 12 h after single and multiple doses
Pharmacokinetics - C24
Plasma concentration observed at time 24 h after single and multiple doses
Pharmacokinetics - Ctrough
Concentration prior to the morning dose on Days 2-14 and prior to the evening dose on Days 2-13
Pharmacokinetics - Cmin
Minimum observed concentration during the dosing interval (between dose time and dose time plus tau) after single and multiple doses of KVD824 with and without food
Pharmacokinetics - Cavg
Average concentration (AUC(0-tau)/tau)
Pharmacokinetics - AUC(0-12)
Area under the curve from time 0 to 12 hours post-dose after single and multiple doses
Pharmacokinetics - AUC(0-12)/Dose
Area under the curve from time 0 to 12 hours post-dose divided by dose
Pharmacokinetics - AUC(0-24)
Area under the curve from time 0 to 24 hours post-dose after single and multiple doses
Pharmacokinetics - AUC(0-24)/Dose
Area under the curve from time 0 to 24 hours post-dose divided by dose
Pharmacokinetics - AUC(0-last)
Area under the curve from time 0 to the time of last measurable concentration after single and multiple doses
Pharmacokinetics - AUC(0-last)/Dose
Area under the curve from time 0 to the time of last measurable concentration divided by dose
Pharmacokinetics - AUC(0-tau)
Area under the curve for the defined interval between doses (tau)
Pharmacokinetics - AUC(0-inf)
Area under the curve from time 0 extrapolated to infinity
Pharmacokinetics - AUC(0-inf)/D
Area under the curve from time 0 extrapolated to infinity divided by dose
Pharmacokinetics - AUCextrap
Area under the curve from time of the last measurable concentration to infinity as a percentage of the area under the curve extrapolated to infinity
Pharmacokinetics - T1/2
Terminal elimination half-life after single and multiple doses of KVD824 with and without food
Pharmacokinetics - Lambda-z
First order rate constant associated with the terminal (log-linear) portion of the curve after single and multiple doses
Pharmacokinetics - CL/F
Total body clearance calculated after a single extravascular administration where F (fraction of dose bioavailable) is unknown
Pharmacokinetics - CL/Ftau
Total body clearance calculated using AUC(0-tau) after repeated extravascular administration, where F (fraction of dose bioavailable) is unknown
Pharmacokinetics - Vz/F
Apparent volume of distribution based on the terminal phase calculated using AUC(0-inf) after a single extravascular administration where F (fraction of dose bioavailable) is unknown
Pharmacokinetics - Vz/Flau
Apparent volume of distribution based on the terminal phase calculated using AUC(0-tau) after extravascular administration where F (fraction of dose bioavailable) is unknown
Pharmacokinetics - Frel Cmax
Relative bioavailability based on Cmax
Pharmacokinetics - Frel AUC(0-12)
Relative bioavailability based on AUC(0-12)
Pharmacokinetics - Frel AUC(0-inf)
Relative bioavailability based on AUC(0-inf)
Pharmacokinetics - AR Cmax
Accumulation ratio based on Cmax repeated dose/Cmax single dose
Pharmacokinetics - Fluctuation
Peak to trough fluctuation (Cmax-Cmin)/Cavg × 100

Secondary Outcome Measures

Safety - Adverse Events
Number of Subjects with Adverse Events
Safety - Serious Adverse Events
Number of Subjects with Serious Adverse Events
Safety - Laboratory Assessments
Number of participants with clinically significant changes in laboratory assessments
Safety - Vital Signs
Number of participants with clinically significant changes in vital signs
Safety - ECG
Number of participants with clinically significant changes in electrocardiogram (ECG) measurements

Full Information

First Posted
October 26, 2021
Last Updated
November 3, 2021
Sponsor
KalVista Pharmaceuticals, Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05118958
Brief Title
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

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
May 19, 2020 (Actual)
Primary Completion Date
December 1, 2020 (Actual)
Study Completion Date
December 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
KalVista Pharmaceuticals, Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Initial open-label crossover (Part 1) followed by double-blind, randomised, placebo-controlled part (Part 3).
Allocation
Randomized
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1 - Period 1 - Prototype 1 600 mg (single dose fasted)
Arm Type
Experimental
Arm Description
600 mg (2 x 300 mg) KVD824 prototype 1 modified-release tablet dosed orally in fasted state as a single dose
Arm Title
Part 1 - Period 3 - Prototype 2 600 mg (single dose fasted)
Arm Type
Experimental
Arm Description
600 mg (2 x 300 mg) KVD824 prototype 2 modified-release tablet dosed orally in fasted state as a single dose
Arm Title
Part 1 - Period 4 - Prototype 1 900 mg (single dose fasted)
Arm Type
Experimental
Arm Description
900 mg (3 x 300 mg) KVD824 prototype 1 modified-release tablet dosed orally in fasted state as a single dose
Arm Title
Part 1 - Period 5 - Prototype 1 600 mg and Prototype 3 300 mg (single dose fasted)
Arm Type
Experimental
Arm 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
Arm Title
Part 1 - Period 6 - Prototype 1 900 mg (single dose fed)
Arm Type
Experimental
Arm Description
900 mg (3 x 300 mg) KVD824 prototype 1 modified-release tablet dosed orally in fed state as a single dose
Arm Title
Part 3 - KVD824 Prototype 1 600 mg (multiple dose fed)
Arm Type
Experimental
Arm 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.
Arm Title
Part 3 - Placebo to KVD824 Prototype 1 600 mg (multiple dose fed)
Arm Type
Placebo Comparator
Arm 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.
Arm Title
Part 3 - KVD824 Prototype 1 900 mg (multiple dose fed)
Arm Type
Experimental
Arm 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.
Arm Title
Part 3 - Placebo to KVD824 Prototype 1 900 mg (multiple dose fed)
Arm Type
Placebo Comparator
Arm 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.
Arm Title
Part 3 - KVD824 Prototype 1 900 mg (multiple dose fasted)
Arm Type
Experimental
Arm 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.
Arm Title
Part 3 - Placebo to KVD824 Prototype 1 900 mg (multiple dose fasted)
Arm Type
Placebo Comparator
Arm 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.
Arm Title
Part 1 - Period 2 - KVD824 IR Capsule 600 mg (single dose fasted)
Arm Type
Active Comparator
Arm Description
600 mg (2 x 300 mg) KVD824 immediate release Capsule dosed orally in fasted state as a single dose
Intervention Type
Drug
Intervention Name(s)
KVD824 Prototype 1 modified-release tablet
Intervention Description
300 mg modified-release tablet
Intervention Type
Drug
Intervention Name(s)
KVD824 Prototype 2 modified-release tablet
Intervention Description
300 mg modified-release tablet
Intervention Type
Drug
Intervention Name(s)
KVD824 Immediate-Release Capsule
Intervention Description
300 mg immediate-release capsule
Intervention Type
Drug
Intervention Name(s)
Placebo to KVD824 Prototype 1
Intervention Description
Placebo to 300 mg KVD824 Prototype 1 modified-release tablet
Intervention Type
Drug
Intervention Name(s)
KVD824 Prototype 3 modified-release tablet
Intervention Description
300 mg modified-release tablet
Primary Outcome Measure Information:
Title
Pharmacokinetics - Tlag
Description
Time prior to the first measurable concentration after single and multiple doses of KVD824
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - Tmax
Description
Time of maximum observed concentration after single and multiple doses of KVD824 with and without food
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - Cmax
Description
Maximum observed concentration after single and multiple doses of KVD824 with and without food
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - Cmax/Dose
Description
Maximum observed concentration divided by dose
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - C12
Description
Plasma concentration observed at time 12 h after single and multiple doses
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - C24
Description
Plasma concentration observed at time 24 h after single and multiple doses
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - Ctrough
Description
Concentration prior to the morning dose on Days 2-14 and prior to the evening dose on Days 2-13
Time Frame
Days 2-14
Title
Pharmacokinetics - Cmin
Description
Minimum observed concentration during the dosing interval (between dose time and dose time plus tau) after single and multiple doses of KVD824 with and without food
Time Frame
Days 2-14
Title
Pharmacokinetics - Cavg
Description
Average concentration (AUC(0-tau)/tau)
Time Frame
Days 2-14
Title
Pharmacokinetics - AUC(0-12)
Description
Area under the curve from time 0 to 12 hours post-dose after single and multiple doses
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - AUC(0-12)/Dose
Description
Area under the curve from time 0 to 12 hours post-dose divided by dose
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - AUC(0-24)
Description
Area under the curve from time 0 to 24 hours post-dose after single and multiple doses
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - AUC(0-24)/Dose
Description
Area under the curve from time 0 to 24 hours post-dose divided by dose
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - AUC(0-last)
Description
Area under the curve from time 0 to the time of last measurable concentration after single and multiple doses
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - AUC(0-last)/Dose
Description
Area under the curve from time 0 to the time of last measurable concentration divided by dose
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - AUC(0-tau)
Description
Area under the curve for the defined interval between doses (tau)
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - AUC(0-inf)
Description
Area under the curve from time 0 extrapolated to infinity
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - AUC(0-inf)/D
Description
Area under the curve from time 0 extrapolated to infinity divided by dose
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - AUCextrap
Description
Area under the curve from time of the last measurable concentration to infinity as a percentage of the area under the curve extrapolated to infinity
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - T1/2
Description
Terminal elimination half-life after single and multiple doses of KVD824 with and without food
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - Lambda-z
Description
First order rate constant associated with the terminal (log-linear) portion of the curve after single and multiple doses
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - CL/F
Description
Total body clearance calculated after a single extravascular administration where F (fraction of dose bioavailable) is unknown
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - CL/Ftau
Description
Total body clearance calculated using AUC(0-tau) after repeated extravascular administration, where F (fraction of dose bioavailable) is unknown
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - Vz/F
Description
Apparent volume of distribution based on the terminal phase calculated using AUC(0-inf) after a single extravascular administration where F (fraction of dose bioavailable) is unknown
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - Vz/Flau
Description
Apparent volume of distribution based on the terminal phase calculated using AUC(0-tau) after extravascular administration where F (fraction of dose bioavailable) is unknown
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - Frel Cmax
Description
Relative bioavailability based on Cmax
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - Frel AUC(0-12)
Description
Relative bioavailability based on AUC(0-12)
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - Frel AUC(0-inf)
Description
Relative bioavailability based on AUC(0-inf)
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - AR Cmax
Description
Accumulation ratio based on Cmax repeated dose/Cmax single dose
Time Frame
Days 1, 10 and 14
Title
Pharmacokinetics - Fluctuation
Description
Peak to trough fluctuation (Cmax-Cmin)/Cavg × 100
Time Frame
Days 1, 10 and 14
Secondary Outcome Measure Information:
Title
Safety - Adverse Events
Description
Number of Subjects with Adverse Events
Time Frame
Change from pre-dose to last visit (up to 14 days)
Title
Safety - Serious Adverse Events
Description
Number of Subjects with Serious Adverse Events
Time Frame
Change from pre-dose to last visit (up to 14 days)
Title
Safety - Laboratory Assessments
Description
Number of participants with clinically significant changes in laboratory assessments
Time Frame
Throughout the trial to last visit (up to 14 days)
Title
Safety - Vital Signs
Description
Number of participants with clinically significant changes in vital signs
Time Frame
Throughout the trial to last visit (up to 14 days)
Title
Safety - ECG
Description
Number of participants with clinically significant changes in electrocardiogram (ECG) measurements
Time Frame
Throughout the trial to last visit (up to 14 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Facility Information:
Facility Name
KalVista Investigative Site
City
Nottingham
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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