Clinical trial NCT01478230: An Exploratory Study Comparing Two Nicotine Inhalers
Official title: A Proof of Concept With a New Nicotine Inhaler in Comparison With Nicotine Inhaler 10 mg
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Tobacco Dependence
Keywords: Pharmacokinetics
Lead sponsor: Johnson & Johnson Consumer and Personal Products Worldwide
Sponsor class: INDUSTRY
First posted: 2011-11-23
Enrollment: 36
Sex: ALL
Minimum age (years): 19
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: Subjects will be screened within 28 days before the first study treatment to confirm that they meet the requirements to participate in the trial. They will return to the site for two treatment visits, at least 12 hours each, and at least one day in between visits. At each visit treatment N1/3-I5 or Nicotine Inhaler 10 mg will be administered every hour for 11 hours. The investigator (or an appropriate delegate at the investigator site) will obtain informed consent from each subject. Blood samples will be drawn on a special schedule. The total predicted amount of blood sampled from each subject is 174 mL over the whole study. Subjects will be required to follow specific smoking and dietary restrictions and rate their urges to smoke, general liking of the product, and how easy the product is to use.

Detailed description: Blood for pharmacokinetic analyses will be drawn prior to the first administration and immediately before administration at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 hours. Thereafter samples will be drawn at 5, 10, 15, 20, 25, 30, 45, and 60 minutes after the 11-hour administration. Easiness of use will be rated using an 8-grade ordered category scale at 10 minutes after the start of administrations at 3, 6, and 9 hours. Overall liking will be rated using an 8-grade ordered category scale at 12 hours. Urges to smoke will be rated on a 4-grade ordered category scale immediately before and at 15 minutes after the first administration, and as well as before and 15 minutes after the start of administrations at 3, 6, and 9 hours, and at 12 hours. Used cartridges will be collected. Pooled samples per subject and treatment will be analyzed to determine the amount of remaining nicotine. Tolerability of the treatments will be evaluated in terms of reported and observed adverse events (AE).

Since the primary objective is to compare steady-state nicotine pharmacokinetics of N1/3-I5 with that of Nicotine Inhaler 10 mg, this study will have a multiple-dose setting. A crossover design has been chosen for this study in order to allow within-subject comparisons of treatments. Healthy habituated adults smoking at least 10 cigarettes daily for at least one year preceding inclusion will be included in the study, since they are expected to tolerate the doses of nicotine that will be administered.

Eligibility criteria: Inclusion Criteria:

* Healthy (per protocol-specified parameters) male or female subjects between the ages of 19 and 50 years, inclusive.
* Smoking of at least 10 cigarettes daily during at least one year preceding inclusion.
* For females: Postmenopausal state or premenopausal/perimenopausal state with a protocol-specified effective means of contraception or declared absence of sexual contact with a male partner during the study.
* For males: No pregnant spouse or partner at screening and willingness to protect potential spouse or partner from becoming pregnant during the study.
* Body Mass Index (BMI) within protocol-specified parameters.
* A personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
* Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures specified in the protocol

Exclusion Criteria:

* Evidence or history of an acute or chronic medical or psychiatric condition or allergy or laboratory abnormality, or of use of drugs that, in the judgment of the investigator or an authorized study physician, may increase the risk associated with study participation or interfere with the interpretability of study results.
* Females: Pregnancy, breast-feeding, premenopausal, or perimenopausal, state with insufficient contraception as specified under Inclusion Criteria.
* Males: Pregnant spouse or partner or no willingness to prevent conception in a spouse or partner.
* History of regular alcohol consumption outside the protocol-specified allowances.
* Treatment with an investigational drug within 3 months preceding the first dose of study treatment.
* Known sensitivity to heparin or history of heparin-induced thrombocytopenia.
* Pathological oral status interfering with normal muscular, sensory, or absorptive function of the oral cavity. Piercing of tongue and lips is considered to impair oral function.
* Relationship to persons involved directly with the conduct of the study, or their families.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: During last dosing interval 11-12 hours post-dose
measure: Average Concentration (Cav)
timeFrame: During last dosing interval 11-12 hours post-dose
measure: Bioavailability [AUCτ]
timeFrame: During last dosing interval 11-12 hours post-dose
Secondary outcomes:
measure: Minimum Observed Plasma Concentration (Cmin)
timeFrame: During last dosing interval 11-12 hours post-dose
measure: Time of Maximum Concentration (Tmax)
timeFrame: During last dosing interval 11-12 hours post-dose
measure: Peak Trough Fluctuation (PTF)
timeFrame: During last dosing interval 11-12 hours post-dose
measure: Swing
timeFrame: During last dosing interval 11-12 hours post-dose
measure: Baseline-corrected Pre-Dosing Plasma Concentration (Cn)
timeFrame: 0 Minutes
measure: Residual Nicotine
timeFrame: 12 hours
measure: Urges to Smoke
timeFrame: During 12 hours
measure: Overall Liking
timeFrame: at 12 hours
measure: Ease of Use
timeFrame: During 9 hours
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: McNeil AB Clinical Pharmacology R&D
Study officials:
affiliation: McNeil AB
name: Elisabeth Kruse, PhD
role: STUDY_DIRECTOR
References: