Healthy volunteers Other
Conditions
Interventions
This was a Phase I, first in human, randomised, double-blind, placebo-controlled study to assess the safety, tolerability, and PK of KH-001 besylate following single ascending (SAD) and multiple ascen
Sponsors
Kanna Health Ltd (trading as Kadence Bio)
Eligibility
Sex/Gender
Male
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Healthy male between 18 and 64 years of age, inclusive 2. For male participants with a female partner of childbearing potential, the contraception requirements for participation required the use of a condom by the male in addition to either one other highly effective method of contraception, or one other effective method of contraception by the female partner, if applicable from first dose until 3 months after last dose 3. Body mass index (BMI) of 18-30 kg/m² 4. No clinically significant history of previous allergy / sensitivity to the investigational medicinal product (IMP) or any of the excipients contained within the IMP(s) 5. No clinically significant abnormal test results for serum biochemistry, haematology and/or urine analyses within 28 days before the first dose administration of the IMP 6. Negative urinary drugs of abuse (DOA) screen (including alcohol) test results, determined within 28 days before the first dose administration of the IMP 7. Negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg)) and hepatitis C virus antibody (HCV Ab) test results at Screening 8. No clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 28 days before first dose of IMP including a PR interval > 220ms, QT interval corrected using Fredericia’s formula QTcF > 450ms 9. No clinically significant abnormalities in vital signs (blood pressure/heart rate, respiratory rate, oral temperature) determined within 28 days before first dose of IMP 10. Available to complete the study (including all follow-up visits) 11. Satisfied an Investigator about participant fitness to participate in the study 12. Provided written informed consent to participate in the study
Exclusion criteria
Exclusion criteria: 1. A clinically significant history of gastrointestinal disorder likely to influence IMP absorption 2. Allergic reaction to the IMP or history of reaction to relevant supplements 3. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 28 days or 5 half-lives (whichever is longer) prior to the first dose of IMP 4. Evidence of any clinically significant history or the presence of renal, hepatic, respiratory, cardiovascular (hypertension, unstable angina, arrhythmia, QT prolongation, etc), metabolic dysfunction, haematological, lymphatic or neurological diseases 5. Disorders of the central nervous system, psychiatric disorders, behavioural disturbances (e.g., cerebrovascular events, depression, post-traumatic stress disorder [PTSD], anxiety, bipolar disorder, severe migraine, Parkinson’s disease) 6. History of narrow angle glaucoma 7. Have had a tattoo or piercing in the 3 months prior to Screening 8. Reported having experienced suicidal ideation (Type 4 or 5 on the Columbia-Suicide Severity Rating Scale [C-SSRS]) within 28 days prior to Screening, any suicidal behaviour within 2 years prior to Screening (Any “Yes” answers on Suicidal Behaviour section of C-SSRS), and/or the Investigator assessed the participant to be a safety risk to him/herself or others 9. Past history of prostate cancer, benign prostatic hyperplasia (BPH) or other clinically significant prostate disease 10. Concomitant disease or condition that could have interfered with, or treatment which may have interfered with, the conduct of the study, or that would, in the opinion of the investigator, have posed an unacceptable risk to the participant in this study 11. Concomitant use of CNS medications (including anti-depressants, anti-psychotics), tramadol, topical anaesthetics, phosphodiesterase 5 (PDE5) inhibitors or vasoactive penile injection therapy 12. A clinically significant current or history of drug or alcohol abuse (defined as the consumption of more than 14 units [for male participants] of alcohol a week) within the past two years 13. Inability to communicate well with the Investigators (i.e., language problem, poor mental development or impaired cerebral function) 14. Participation in a New Chemical Entity (NCE) clinical study within the previous 3 months or five half-lives, whichever is longer, or a marketed drug clinical study within the 30 days or five half-lives, whichever is longer, before the first dose of IMP. (Washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study) 15. Donation of 450 mL or more blood within the 3 months before the first dose of IMP 16. Vegans, vegetarians or other dietary restrictions (e.g., restrictions for medical, religious or cultural reasons, etc). Participants who preferred vegetarian options can be included if willing to follow available clinic meal options and all study procedures 17. Users of nicotine products i.e., current smokers or ex-smokers who have smoked within the 6 months prior to Screening or users of cigarette replacements (i.e., e-cigarettes, nicotine patches or gums) 18. Participants who received a COVID-19 vaccine injection within 28 days prior to the first dose of IMP 19. Participants with pregnant or breastfeeding partners 20. Clinically significant maxillofacial pathology, tongue piercings in the 3 months prior to Screening (Formulation Effect only)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoints for this study were safety endpoints and were defined as follows: - Adverse Events - Laboratory safety (biochemistry, haematology, coagulation and urinalysis) - Vital signs (systolic/diastolic blood pressure, heart rate, respiration rate, and oral temperature) - 12 lead ECG (heart rate, RR interval, PR interval, QRS width, QT interval, and QTcF interval) Timepoints for Assessment were as follows: Adverse Events AEs were recorded from the point of informed consent up to final post-study follow up visit. Laboratory Safety Testing SAD and Formulation Effect: Screening, Day -1, Day 2 (of each treatment period), and post study MAD: Screening, Day -1, Day 2, Day 4, Day 6 and post study Vital Signs SAD and Formulation Effect: Screening, Day -1, Day 1 (5 timepoints up to 24 hr post-dose of each treatment period), and post study MAD: Screening, Day -1, Day 1 and Day 5 (4 timepoints up to 24 hr post-dose), Days 3-4 (pre-dose) and post study 12-Lead ECG SAD and Formulation Effect: Screening, Day 1 (4 timepoints up to 24 hr post-dose of each treatment period), and post study MAD: Screening, Day 1 and Day 5 (4 timepoints up to 24 hr post-dose), Day 4 (pre-dose) and post study | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints for this study were pharmacokinetic parameters derived from analysis of plasma samples for concentrations of KH-001. Endpoints were defined as follows: SAD: Plasma PK parameters included AUC0-t, Cmax and Tmax MAD: Day 1: Plasma PK parameters included AUC0-t, Cmax and Tmax - Day 5: Plasma PK parameters included AUC0-t, Cmax, and Tmax Formulation Effect: PK parameters included AUC0-t, Cmax and Tmax Timepoints for Assessment were as follows: Plasma PK Sampling: Parts A & D: Day 1 (17 timepoints from pre-dose to 24 hours post-dose), each treatment period Part B: Days 1 and 5 (13 timepoints from pre-dose to 12 hours post-dose), Day 2-4 (5 timepoints from pre-dose to 8 hours post-dose) and Day 6 | — |
Countries
United Kingdom, Wales
Contacts
Public ContactHans-Jürgen Gruss
Outcome results
None listed