E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Nicotine withdrawal symptoms |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to compare the steady-state nicotine pharmacokinetics (as described by the maximum observed nicotine plasma concentration, Cmax; average nicotine plasma concentration, Cav; and the area under the nicotine plasma concentration-vs.-time curve, AUCt during the last dosing interval) of Nicotine Short Filter 1/3 Inhaler 5 mg (N1/3-I5) given every hour with that of Nicotine Inhaler 10 mg given every hour. |
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E.2.2 | Secondary objectives of the trial |
•to further describe the steady-state nicotine pharmacokinetics with respect to the time to Cmax (tmax), the minimum observed nicotine plasma concentration (Cmin), the peak-trough fluctuation (PTF), and the swing during the last dosing interval,
•to compare treatments with respect to baseline-corrected nicotine plasma concentrations immediately before each user session (Cn),
•to compare treatments with respect to easiness of use,
•to compare treatments with respect to overall liking,
•to assess urges to smoke at specified time points during both treatments,
•to compare treatments with respect to the amounts of nicotine released from N1/3-I5 and Nicotine Inhaler 10 mg,
•to evaluate the tolerability of the treatments in terms of reported and observed adverse events (AE).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Healthy male or female subjects between the ages of 19 and 50 years, inclusive. Health is defined as the absence of clinically relevant abnormalities, as judged by the investigator or an authorized physician on the basis of a detailed medical history, physical examination, blood pressure and pulse rate measurements, 12-lead electrocardiogram as well as clinical laboratory tests. The responsible physician may request additional investigations or analyses if considered necessary.
2.Smoking of at least 10 cigarettes daily during at least one year preceding inclusion.
3.For females: Postmenopausal state (absence of menstrual discharge for at least two years and a serum FSH level exceeding 30 IU/L) or premenopausal/perimenopausal state with an effective means of contraception (oral, injected or implanted hormonal contraceptives, intrauterine device, or status after operative sterilization), 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.
4.Body Mass Index (BMI) between 17.5 and 30.0 kg/m2 and a total body weight more or equal to 55.0 kg.
5.A personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
6.Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures specified in the protocol.
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E.4 | Principal exclusion criteria |
1.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.
2.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.
3.History of regular alcohol consumption in the 6 months before screening exceeding weekly limits of 2 L of wine or 5 L of beer or 0.6 L of spirits for females and 3 L of wine or 7.5 L of beer or 0.9 L of spirits for males. The investigator may lower these limits if a subject consumes different types of alcoholic beverages.
4.Treatment with an investigational drug within 3 months preceding the first dose of study treatment.
5.Donation or loss of blood within 3 months prior to the first treatment visit if the estimated lost blood volume equaled or exceeded 450 mL.
6.Known sensitivity to heparin or history of heparin-induced thrombocytopenia.
7.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.
8.Relationship to persons involved directly with the conduct of the study (i.e., principal investigator, subinvestigators, study coordinators, other study personnel, employees or contractors of the sponsor or Johnson & Johnson subsidiaries, and the family of each).
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints are the maximum observed concentration (Cmax) and the average concentration (Cav) during the last dosing interval, and the area under the nicotine plasma concentration-vs.-time curve during the last 60-minute dosing interval (AUCt).
The dosing interval (t) in this study will be one (1) hour. Consequently, Cav will have the same value as AUCt (but with a different unit), since Cav is calculated as AUCt divided by t. Therefore Cav will not be displayed in the report, only AUCt.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
11 hours, 11 hours and 5 minutes, 11 hours and 10 minutes, 11 hours and 15 minutes, 11 hours and 20 minutes, 11 hours and 25 minutes, 11 hours and 30 minutes, 11 hours and 45 minutes, and 12 hours after start of the first administration. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are time to Cmax (tmax), the minimum observed concentration (Cmin), the peak-trough fluctuation (PTF) and the swing during the last dosing interval, subjects ratings of easiness of use, overall liking and urges to smoke, released amount of nicotine from inhalers, and the occurrence of adverse events (AEs).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pharmacokinetic: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 hours, 11 hours and 5 minutes, 11 hours and 10 minutes, 11 hours and 15 minutes, 11 hours and 20 minutes, 11 hours and 25 minutes, 11 hours and 30 minutes, 11 hours and 45 minutes, and 12 hours after start of the first administration.
Easiness of use: 10 minutes after the start of administrations at 3, 6, and 9 hours.
Overall liking: 12 hours
Urges to smoke: 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
exploratory comparison of different formulations |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study is defined as the last visit of the last subject. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |