A Single Dose Safety, Tolerability, Pharmacokinetic and Food Effect Study of KVD900 in Healthy Volunteers

Study Overview
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Brief Summary
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A safety, tolerability, pharmacokinetic and food effect study of KVD900 in healthy volunteers.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of KVD900 Followed by Crossover Sub-studies of KVD900 Formulations, and Food Effect in Healthy Male Volunteers

Conditions
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Hereditary Angioedema

Intervention / Treatment
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* Drug: KVD900
* Drug: Placebo to KVD900


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects between 18 and 55 years of age. Healthy subjects as determined by past medical history and as judged by the Chief Investigator or designee. Male subject willing to use a highly effective method of contraception. Subject with a body mass index (BMI) of 18-32 kg/m2. Subject with no clinically significant history of previous allergy or sensitivity to KVD900 or any of the excipients contained within the investigational medicinal product (IMP). Subject with no clinically significant abnormal serum biochemistry, haematology, clotting profiles, and urine examination values within 28 days before the first dose of IMP. Subject with a negative urinary drugs of abuse screen, determined within 28 days before the first dose of IMP Subject with negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results. Subject with no clinically significant abnormalities in 12-lead electrocardiogram Subjects must not donate sperm from first dose until at least 3 months after last dose of IMP. Subjects without any special food restrictions that would hinder ability to consume the high fat breakfast provided during study Part C; such as lactose intolerance , vegan, low-fat, low sodium, etc. Subjects with no known allergy or sensitivity to lactose and/or any additional excipients contained in IMP. Subject must be available to complete the study (including all follow up visits). Subject must satisfy the Chief Investigator or designee about their fitness to participate in the study. Subject must provide written informed consent to participate in the study. Exclusion Criteria: A clinically significant history of gastrointestinal disorder likely to influence IMP absorption. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements . Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular (no history of syncope or vasovagal events), or metabolic dysfunction. Subjects with a history of clotting abnormalities. A clinically significant history of drug or alcohol abuse in the last 5 years. Users of nicotine products i.e., current smokers or ex-smokers who have smoked within the 6 months prior to dosing with the study medication or users of cigarette replacements. Inability to communicate well with Investigators. Participation in a New Chemical Entity clinical study within the previous 3 months or a marketed drug clinical study within the 30 days before the first dose of IMP. Donation of 450 mL or more blood within the 3 months before the first dose of IMP.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose - 5 mg<br> | Drug: KVD900<br>* Active<br>Drug: Placebo to KVD900<br>* Placebo<br>|
| Experimental: Single Ascending Dose - 10 mg<br> | Drug: KVD900<br>* Active<br>Drug: Placebo to KVD900<br>* Placebo<br>|
| Experimental: Single Ascending Dose - 20 mg<br> | Drug: KVD900<br>* Active<br>Drug: Placebo to KVD900<br>* Placebo<br>|
| Experimental: Single Ascending Dose - 40 mg<br> | Drug: KVD900<br>* Active<br>Drug: Placebo to KVD900<br>* Placebo<br>|
| Experimental: Single Ascending Dose - 80 mg<br> | Drug: KVD900<br>* Active<br>Drug: Placebo to KVD900<br>* Placebo<br>|
| Experimental: Single Ascending Dose - 160 mg<br> | Drug: KVD900<br>* Active<br>Drug: Placebo to KVD900<br>* Placebo<br>|
| Experimental: Single Ascending Dose - 300 mg<br> | Drug: KVD900<br>* Active<br>Drug: Placebo to KVD900<br>* Placebo<br>|
| Experimental: Single Ascending Dose - 600 mg<br> | Drug: KVD900<br>* Active<br>Drug: Placebo to KVD900<br>* Placebo<br>|
| Experimental: Formulation Screen<br> | Drug: KVD900<br>* Active<br>|
| Experimental: Food Effect<br> | Drug: KVD900<br>* Active<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects with Adverse Events |  | Change from pre-dose to last visit, 5-7 days post dose. | 
| Number of Subjects with Serious Adverse Events |  | Change from pre-dose to last visit, 5-7 days post dose. | 
| Number of participants with clinically significant changes in laboratory assessments |  | Throughout study until last visit, 5-7 days post dose. | 
| Number of participants with clinically significant changes in vital signs |  | Throughout study until last visit, 5-7 days post dose. | 
| Number of participants with clinically significant changes in electrocardiogram (ECG) measurements |  | Throughout study until last visit, 5-7 days post dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics - Cmax | Derived from time-concentration plasma levels of KVD900 | Up to 48 hours post dose | 
| Pharmacokinetics - AUC0-t | Derived from time-concentration plasma levels of KVD900 | Up to 48 hours post dose | 
| Pharmacokinetics - AUC0-24 | Derived from time-concentration plasma levels of KVD900 | Up to 24 hours post dose | 
| Pharmacokinetics - AUC0-inf | Derived from time-concentration plasma levels of KVD900 | Up to 48 hours post dose | 
| Pharmacokinetics - food effect (Part C only) | 90% confidence intervals of the ratios for AUC0-t and Cmax with and without food lie in the range 80-125 | Up to 24 hours post dose | 
| Pharmacokinetics - formulation bridge - relative bioavailability (Part B only) | 90% confidence intervals of the ratios for AUC0-t and Cmax between the two dosages lie in the range 80-125 | Up to 24 hours post dose |