Pharmacokinetics and Acute Effects of Multiple Dose of Nicotine: Electronic Cigarette and Cigarette

Pharmacokinetics and Acute Effects of Multiple Dose of Nicotine Administered by Electronic Cigarette and Cigarette

The purposes of this study are 1) to determine the pharmacokinetics of nicotine after multiple dose administration by electronic cigarette and 2) to compare the acute effects of multiple dose of nicotine administrated by electronic cigarette compared with those obteined by cigarette.

Study Overview

• Status: Completed
• Conditions: Nicotine Use Disorder
• Intervention / Treatment: Drug: Nicotine

Detailed Description

Electronic cigarettes (e-cigarettes) are battery-operated devices that deliver nicotine via inhaled vapour or "vaping". At present, e-cigarettes are becoming increasingly popular among smokers worldwide. However, knowledge about e-cigarette nicotine pharmacology remains limited.

The aims of this study are 1) to determine the pharmacokinetics of nicotine after multiple dose administration by electronic cigarette and 2) to compare the acute effects of multiple dose of nicotine administrated by electronic cigarette compared with those obteined by cigarette.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Institut Hospital del Mar d'Investigacions Mèdiques-IMIM. Parc de Salut Mar.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Understanding and accepting the study procedures and signing the informed consent.
• Male adults volunteers (18-45 years old).
• Clinical history and physical examination demonstrating no organic or psychiatric disorders.
• The ECG and general blood and urine laboratory tests performed before the study should be within normal ranges. Minor or occasional changes from normal ranges are accepted if, in the investigator's opinion, considering the current state of the art, they are not clinically significant, are not life-threatening for the subjects and do not interfere with the product assessment. These changes and their non-relevance will be justified in writing specifically.
• Present use of nicotine without serious adverse reactions.
• Smokers ≥ 3 cigarettes/day.

Exclusion Criteria:

• Having suffered any cardiovascular and/or respiratory disease in the three months prior to the study start.
• History of drug dependence (except for nicotine dependence).
• Daily consumption >4 standard units of ethanol.
• Regular use of any drug in the month prior to the study sessions. The treatment with single or limited doses of symptomatic medicinal products in the week prior to the study sessions will not be a reason for exclusion if it is calculated that it has been cleared completely the day of the experimental session.
• Having suffered any organic disease or major surgery in the three months prior to the study start.
• Blood donation 12 weeks before or participation in other clinical trials with drugs in the previous 12 weeks.
• History or clinical evidence of gastrointestinal, liver, renal or other disorders which may lead to suspecting a disorder in drug absorption, distribution, metabolism or excretion, or that suggest gastrointestinal irritation due to drugs.
• Subjects unable to understand the nature, consequences of the study and the procedures requested to be followed.
• Use of any drug or substance inhibitor of cytochrome P-450-1A6 (CYP1A6) (p.e. raloxifene, coumarins, etc)

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Electronic cigarette; Multiple dose Nicotine 0.8 mg, administrated by electronic cigarette (10 puffs) + Nicotine 0.8 mg, administrated by electronic cigarette (10 puffs) separated by 60 minutes	Drug: Nicotine; Multiple dose nicotine; Other Names: Marlboro®
Active Comparator: Cigarette; Multiple dose Nicotine 0.8 mg, administrated by cigarette (10 puffs) + Nicotine 0.8 mg, administrated by cigarette (10 puffs) separated by 60 minutes	Drug: Nicotine; Multiple dose nicotine; Other Names: Marlboro®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve (AUC 0-24h)	Calculation of AUC of the concentrations of nicotine and its metabolites in blood	From baseline (pre-dose, 0h) to 5, 15, 30, 45, 55, 65, 75, 90, 105, 120 and 24h post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve (AUC 0-24h)	Calculation of AUC of the concentrations of nicotine and its metabolites in urine	From baseline (pre-dose, 0h) to 55, 120 min, 6, 12 and 24h
Area Under the Concentration-Time Curve (AUC 0-24h)	Calculation of AUC of the concentrations of nicotine and its metabolites in oral fluid	From baseline (pre-dose, 0h) to 15, 30, 45, 55, 65, 75, 90, 105, 120 min, 6, 12 and 24h
Number of Participants with Serious and Non-Serious Adverse Events	Collection of adverse effects spontaneously reported by the participants and/or observed by the investigators	2 days after each substance administration
Elimination half-life	Calculation of elimination hal-life from concentrations of nicotine and its metabolites in plasma-blood, urine and oral fluid.	From baseline to 24h post-dose
Changes in blood pressure	Measure of blood pressure (systolic and diastolic blood pressure)	From pre-dose (baseline) to 120 min post-dose
Changes in heart rate	Measure of heart rate (pulse)	From pre-dose (baseline) to 120 min post-dose
Changes in expired carbon monoxide (CO) aire	Measure of expired CO aire using a BreathCO monitor	From pre-dose (baseline) to 120 min post-dose
Changes in pupil diameter	Measure of pupil diameter using a Haab pupil gauge	From pre-dose (baseline) to 120 min post-dose
Changes in oral temperature	Measure of temperature in mouth using automatic thermometer	From pre-dose (baseline) to 120 min post-dose
Changes in subjective effects	Subjective effects will be measured using rate scales (visual analogue scales) including measures of good effects and other feelings induced by nicotine	From pre-dose (baseline) to 120 min post-dose
Changes in nicotine abstinence symptoms	Nicotine abstinence symptoms will be measured using rate scales (visual analogue scales) including items sensitive to nicotine effects	From pre-dose (baseline) to 120 min post-dose

Collaborators and Investigators

• Sponsor: Parc de Salut Mar
• Collaborators: Istituto Superiore di Sanità
• Investigators: Principal Investigator: Magí Farré, MD, PhD, Parc de Salut Mar

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: July 28, 2015
• First Submitted That Met QC Criteria: July 28, 2015
• First Posted (Estimate): July 30, 2015

Study Record Updates

• Last Update Posted (Estimate): July 30, 2015
• Last Update Submitted That Met QC Criteria: July 28, 2015
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Nicotine; Cigarette; Electronic cigarette
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: IMIMFTCL/CIG-E/1