Smoking cessation and nicotine replacement therapies (NRT) Not Applicable
Conditions
Interventions
This is a single centre, Phase I, randomised, open-label 3-way crossover study of nicotine delivery conducted in healthy male smokers. The duration of study participation is approximately 5 weeks for
Sponsors
Ventus Medical Limited
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Healthy male participants, aged between 21 and 65 years old, inclusive 2. Participant with a body mass index (BMI) of 18-32 kg/m2. BMI = body weight (kg) / [height (m)]2 3. Participants must be current conventional, factory-made cigarette smokers (approximately 10 to 20 cigarettes per day for at least two consecutive years, defined by a positive urine cotinine result of = 200 ng/ml and = 7 ppm exhaled CO breath test (Smokerlyser) at Screening) or participants who have been consistent dual users of conventional cigarettes and e-cigarettes/vape for 12 months, who are not intending to make a quit attempt during the study 4. Participants will be willing to use the study products ENHALE Electronic Inhaler with ENHALE 0.5 mg Nicotine Inhalation Cartridge, Nicorette® Inhalator and Nicorette® QuickMist and use only the products provided to them and abstain from regular cigarette use during clinical confinement (participants are allowed to smoke ad libitum on Day -1 until 12 hours prior to planned first nicotine administration on Day 1) 5. No clinically significant history of previous allergy/sensitivity to nicotine, ENHALE Electronic Inhaler with ENHALE 0.5 mg Nicotine Inhalation Cartridges, Nicorette® Inhalator and Nicorette® QuickMist or any of the excipients contained within the investigational products 6. 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 7. Negative urinary drugs of abuse (DOA) screen (including alcohol) test results, determined within 28 days before the first dose administration of the IMP (N.B.: A positive test result may be repeated at the Investigator’s discretion) 8. Participant with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg)) and hepatitis C virus antibody (HCV Ab) test results at Screening 9. No clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 28 days before first dose of IMP including heart rate, PR interval QRS width and QT interval corrected using Fredericia’s formula (QTcF) 10. No clinically significant abnormalities in vital signs (e.g., blood pressure, heart rate, respiration rate, oral temperature) determined within 28 days before first dose of IMP 11. Participants must be available to complete the study (including all follow-up visits) 12. Participants must satisfy an Investigator about their fitness to participate in the study 13. Participants must provide written informed consent to participate in the study 14. Participants must be willing to comply with all relevant study restrictions including; avoiding strenuous exercise completely from 3 days before the first dose until the final study visit; limiting alcohol consumption to a maximum of 2 units per day from 7 days prior to the first administration of investigational medicinal product (IMP) and avoid alcohol completely for a period of not less than 2 days prior to the first administration of IMP and throughout the study period and; avoiding food or drink containing caffeine, including coffee, tea, cola, energy drinks or chocolates completely from 2 days prior to dosing and during the study
Exclusion criteria
Exclusion criteria: 1. Participants who use roll-your-own cigarettes. or are sole e-cigarette/vape users 2. Participants who have had any treatment with smoking cessation medications (e.g., Bupropion, Champix or any NRTs) within 8 weeks of the planned first nicotine dosing occasion 3. Participants who, prior to enrolment, are planning to quit smoking in the next 12 months. All participants will be informed that they are free to quit smoking and withdraw from the study at any time 4. Participants who have an acute illness (e.g., respiratory tract infection) requiring treatment within 4 weeks prior to first dose 5. 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, with the exception of paracetamol (which may be taken as an analgesic to a maximum of 2 g in 24 h) and ibuprofen (which may be taken as an analgesic to a maximum of 1.2 g in 24 h (400 mg 3 times a day)) 6. Evidence of renal, hepatic, central nervous system, respiratory (including COPD), cardiovascular or metabolic dysfunction 7. A clinically significant history of drug or alcohol abuse (defined as the consumption of more than 21 units of alcohol a week) within the past two years 8. Inability to communicate well with the Investigators (i.e., language problem, poor mental development or impaired cerebral function) 9. Participation in any other clinical study of an investigational product 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). 10. Donation of 450 mL or more blood within the 3 months before the first dose of IMP 11. Vegans, vegetarians or other dietary restrictions (e.g., restrictions for medical, religious or cultural reasons, etc.) 12. Participants who have received a COVID-19 vaccine injection within 14 days prior to first dose of IMP
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoints for this study are pharmacokinetic parameters derived from the analysis of plasma samples for the concentration of nicotine. 1. The following non-compartmental pharmacokinetic parameters will be calculated for the 1st administration of nicotine: 1.1. Cmax, 0-tau - The maximum plasma concentration of nicotine observed over the dosing interval (i.e., 60 minutes) 1.2. pAUC0-tau - The partial area under the concentration-time curve calculated using the trapezoidal rule observed over the dosing interval (i.e., 60 minutes). 2. The following non-compartmental pharmacokinetic parameters will be calculated for the fifth hourly administration of nicotine: 2.1. Cmax, lastdose-t - The maximum plasma concentration of nicotine observed from the last administration to the last measurable concentration 2.2. pAUClast dose-t - The partial area under the concentration-time curve calculated using the trapezoidal rule from the last administration to last measurable concentration. 3. Blood samples for PK analysis of nicotine will be taken at the following timepoints: 3.1. Days 1-3 3.2. First administration: pre-dose and at 2, 4, 6, 8, 10, 12, 15, 20, 30, and 60 min post-dose 3.3. Second, third and fourth hourly administrations: pre-dose and at 10 minutes post-dose 3.4. Fifth administration pre-dose and at 2, 4, 6, 8, 10, 12, 15, 20, 30, and 60 min post-dose and 2, 4, 8 and 19 hours post-dose | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints for this study are pharmacokinetic parameters derived from the analysis of plasma samples for the concentration of nicotine and safety endpoints. 1. Secondary (pharmacokinetic) variables for assessment endpoints are defined as follows. The following non-compartmental pharmacokinetic parameters will be calculated for the fifth hourly administration of nicotine: 1.1. AUC0-8 - The area under the concentration-time curve extrapolated to infinity from dosing time, based on the last measurable concentration 1.2. AUC0-8 - The area under the concentration-time curve calculated using the trapezoidal rule from the time of dosing to 8 hours post-dose 1.3. AUC% extrapolated - Percentage of AUC0-inf due to extrapolation from last observed concentration to infinity 1.4. Tmax - The time to maximum observed plasma nicotine concentration (also calculated for the 1st administration of nicotine 1.5. t½ - The terminal half-life calculated from the terminal slope of the log concentration-time curve as log(2)/slope 1.6. ?z - Elimination rate constant 2. The following pharmacokinetic parameters will be calculated for each hourly nicotine administration 1 to 5: 2.2. Ctrough - The plasma concentration of nicotine immediately prior to each administration 2.3. Cn - The plasma concentration of nicotine at each planned nominal timepoint post each nicotine administration 3. Secondary (safety) variables for assessment are adverse events, vital signs (as measured by systolic blood pressure, diastolic blood pressure and heart rate, respiration rate and oral temperature), ECG test results and laboratory test results. The safety endpoints: 3.1. Adverse events (AEs) 3.2. Laboratory safety (biochemistry, haematology and urinalysis) 3.3. Vital signs (systolic/diastolic blood pressure, heart rate, respiration rate, oral body temperature) 3.4. 12 lead ECG (heart rate, PR interval, QRS duration, QT interval and QTcF interval) 4. Exploratory (pharmacodynamic) variables for ass | — |
Countries
United Kingdom, Wales
Contacts
Public ContactDavid Lawson
Outcome results
None listed