Healthy volunteers. The intended indication for the product under development is damage to secondary organs during a systemic inflammatory response. Not Applicable
Conditions
Interventions
The study is in two parts: Part A (single doses) and Part B (a single dose followed by a continuous slow injection).
In Part A, up to 24 participants will be enrolled in two groups of
we plan to increase the dose as the study progresses. The researchers plan to give the following doses: Group A1 will receive 0.05 mg in their first study session, 0.25 mg in their second session, and
Group A2 will receive 2.5 mg in their first study session, 7.5 mg in their second session, and 20 mg in their third session. Subsequent higher doses will only be tested if the previous dose causes no
Sponsors
Kynos Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female volunteers aged 18-55 years 2. Body mass index (BMI) of 18.5 to 32 kg/m² 3. Body weight >50 kg 4. Deemed healthy on the basis of medical history, clinical laboratory test results, vital sign measurements, ECG, and physical examination 5. Agree to follow the contraception requirements of the trial 6. Male participants must refrain from donating sperm during the treatment period and for at least 90 days following the last dose 7. Able to give fully informed consent
Exclusion criteria
Exclusion criteria: 1. Not healthy (clinically significant abnormality in our screening tests, which include ECG, vital signs, physical examination, and laboratory safety tests of blood and urine) 2. A current or chronic history of liver disease or known hepatic or biliary abnormalities; history of or current evidence of cardiac arrhythmia, structural or mechanical heart disease, or cardiac conduction defect; a history or current evidence of depression, bipolar, suicidal ideation and behaviour; positive tests for hepatitis B and/or C, or human immunodeficiency virus (HIV) 3. Have used any prescription or over-the-counter medications (except paracetamol [up to 2 g per day]), including herbal or nutritional supplements, within 7 days (or 14 days if the medication is a potential enzyme inducer) before the first dose of study medicine; consumed grapefruit or grapefruit juice, Seville oranges or Seville orange-containing products (e.g., marmalade), exotic citrus fruits, red wine, or fruit juices from 7 days before the first dose of study medicine; consumed caffeine- or xanthine-containing products within 24 hours before the first dose of study medicine. 4. Have had a serious reaction to any medicine or have certain food allergies 5. Current smoker or used nicotine containing products within 6 months of screening; a history of alcohol abuse or drug addiction; strenuous activity within 48 hours of the first dose 6. Donated blood or have taken part in a study of an experimental medicine in the 3 months before first admission to the unit, or plan to do so in the 3 months after this study 7. Pregnant or lactating
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Safety and tolerability of KNS366, including vital signs (blood pressure, heart rate, tympanic temperature, and respiratory rate), 12-lead electrocardiogram (ECG), physical examination, laboratory safety tests (haematology, clinical chemistry, and urinalysis), and local tolerability assessments, will be measured regularly by standard Phase I unit monitoring, at screening, Day -1 to Day 4 (Part A), Day -1 to Day 11 (Part B), and at follow-up visits. 2. Treatment-emergent adverse events (TEAEs) to assess tolerability of KNS366 will be collected by often asking volunteers how they are feeling, from the start of the trial until follow-up. 3. In Part B only, mood and cognition will be assessed using the Columbia-Suicide Severity Rating Scale questionnaires and cognitive assessments will be performed to evaluate cognitive and behavioural effects at screening, Days -1, 3, 7 and 11 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetic parameters of KNS366: 1.1. Plasma concentrations of KNS366 after single and repeated doses will be measured by liquid chromatography coupled with tandem mass spectrometry at the following timepoints: between Day 1 and Day 4 in each session in Part A; and between Day 1 and Day 11 in Part B. 1.2. Pharmacokinetics of KNS366 in urine after single and repeated doses will be measured by liquid chromatography coupled with tandem mass spectrometry. Urine samples will be taken at the following timepoints: on Day -1 to Day 4 in each session in Part A; before dosing and from Day 3 to Day 4 in Part B. 2. Pharmacodynamic parameters of KNS366: Blood samples for assay of kynurenine and metabolites will be taken on Day 1 to Day 4 in each session in Part A; and between Day 1 and Day 11 in Part B. | — |
Countries
England, United Kingdom
Outcome results
None listed