Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Exploratory THS 2.1 Nicotine Pharmacokinetics and Safety Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Philip Morris Products S.A.
ClinicalTrials.gov Identifier:
NCT01780688
First received: January 15, 2013
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

The main goal of this exploratory study is to evaluate the pharmacokinetic profile of nicotine for the candidate modified risk tobacco product THS 2.1 and for conventional cigarettes (CC).


Condition Intervention
Smoking
Other: Conventional cigarettes (CC)
Other: THS 2.1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Single-center, Open-label, Randomized, Controlled, Crossover Study to Explore the Nicotine Pharmacokinetic Profile and Safety of Tobacco Heating System (THS) 2.1 Compared to Conventional Cigarettes Following Single and ad Libitum Use in Smoking, But Otherwise Healthy Subjects.

Resource links provided by NLM:


Further study details as provided by Philip Morris Products S.A.:

Primary Outcome Measures:
  • Nicotine Cmax [ Time Frame: Single use (1 day) ] [ Designated as safety issue: No ]
    Maximum plasma concentration (Cmax)

  • Nicotine AUC [ Time Frame: Single use (1 day) ] [ Designated as safety issue: No ]
    Nicotine plasma concentration, area under the curve (AUCt)


Secondary Outcome Measures:
  • Nicotine concentrations [ Time Frame: Single use (1 day); multiple use (1 day) ] [ Designated as safety issue: No ]
    Time course of plasma nicotine concentration

  • Questionnaire of smoking urges (brief version) (QSU-brief) [ Time Frame: single use (1 day); multiple use (1 day) ] [ Designated as safety issue: No ]
    QSU-brief measuring subjective effects of smoking

  • Safety monitoring [ Time Frame: 7 days + 7 days follow-up ] [ Designated as safety issue: Yes ]
    Monitoring of adverse events, based on clinical and laboratory evaluation

  • Nicotine tmax [ Time Frame: Single use (1 day) ] [ Designated as safety issue: No ]
    Time to maximal nicotine concentration in plasma

  • Cough Visual Analog Scale [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Visual Analog Scale on cough

  • Modified Cigarette Evaluation Questionnaire (MCEQ) [ Time Frame: single use (1 day); multiple use (1 day) ] [ Designated as safety issue: No ]
    MCEQ measuring effects of smoking


Enrollment: 190
Study Start Date: May 2012
Study Completion Date: December 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: smoking conventional cigarettes (CC)
After a 1-day nicotine deprivation, subjects are smoking one single cigarette (usual own brand) on one day and then smoking ad libitum on the subsequent day
Other: Conventional cigarettes (CC)
Subjects are randomized in a 1:1 fashion to be assigned to one of the 2 sequences, either A) CC and then THS 2.1, or B) THS 2.1 and then CC.
Other: THS 2.1
Subjects are randomized in a 1:1 fashion to be assigned in one of the sequences, either A) CC and then THS 2.1, or B) THS 2.1 and then CC
Experimental: using the Tobacco Heating System 2.1 (THS 2.1)
After a 1-day nicotine deprivation, subjects are puffing one single tobacco stick using the THS 2.1 on one day and then puffing ad libitum on the subsequent day
Other: Conventional cigarettes (CC)
Subjects are randomized in a 1:1 fashion to be assigned to one of the 2 sequences, either A) CC and then THS 2.1, or B) THS 2.1 and then CC.
Other: THS 2.1
Subjects are randomized in a 1:1 fashion to be assigned in one of the sequences, either A) CC and then THS 2.1, or B) THS 2.1 and then CC

Detailed Description:

This 2-period 2-sequence cross-over clinical study intends to explore the profile of nicotine uptake (rate and extent of nicotine absorbed and associated variability) in healthy smokers switching from (CC) to THS 2.1 (single or ad libitum use) compared to smokers continuing to use CC, as a comparator. This study will serve to optimize blood sampling schedules and sample size estimation for further studies. This study will also provide preliminary information on the relationship between nicotine absorption and urge to smoke/withdrawal symptoms when using THS 2.1 as compared to CC, as well as the safety profile, which is related to the use of THS 2.1.

After screening, enrolled subjects will be admitted to the clinic for 8 days. This study duration includes 2 consecutive periods. Each period consists of 1 day for single use of the product preceded by a 24-hour nicotine deprivation, and 1 day for ad libitum product use. After leaving the clinic, the subjects will be followed up for safety over a period of 7 days.

This clinical study will be conducted in compliance with International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH Good Clinical Practice), the Declaration of Helsinki as amended in 2008, and the applicable regulatory requirements.

  Eligibility

Ages Eligible for Study:   23 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subject has signed an informed consent form before commencement of study procedures
  • Healthy Caucasian aged between 23 to 65 years
  • Subject is current smoker for at least 3 years (based on self-reporting and biochemically verified), who, for the last 4 weeks, had smoked at least 10 commercially available non-mentholated CC per day, and is not planning to make a quit attempt within the next 3 months

Exclusion Criteria:

  • As per Investigator judgment, the subject should not participate in the study for any reason (e.g. medical, psychiatric and/or social reason)
  • The subject has a medical condition requiring smoking cessation, or has a clinically relevant disease / condition which could interfere with the study participation and/or study results
  • The subject has participated in a clinical study within 3 months prior to the Screening Visit
  • Pregnant or lactating woman, and for woman of childbearing potential, absence / refusal to use an acceptable method of effective contraception
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01780688

Locations
United Kingdom
Celerion, 22-24 Lisburn Road
Belfast, United Kingdom, BT9 AD6
Sponsors and Collaborators
Philip Morris Products S.A.
Investigators
Principal Investigator: Adrian J Stewart, MD Celerion, Belfast, Northern Ireland
  More Information

No publications provided

Responsible Party: Philip Morris Products S.A.
ClinicalTrials.gov Identifier: NCT01780688     History of Changes
Other Study ID Numbers: ZRHX-PK-02
Study First Received: January 15, 2013
Last Updated: June 18, 2014
Health Authority: IEC: UK

Keywords provided by Philip Morris Products S.A.:
Modified risk tobacco product (MRTP)
Smoking
Nicotine profile

Additional relevant MeSH terms:
Nicotine
Autonomic Agents
Cholinergic Agents
Cholinergic Agonists
Ganglionic Stimulants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Nicotinic Agonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 23, 2014