Nicotine Pharmacokinetic Profile and Safety of the Tobacco Heating System 2.2 Menthol (THS 2.2 Menthol)

• ClinicalTrials.gov Identifier: NCT01967719
• Recruitment Status: Completed
• First Posted: October 23, 2013
• Results First Posted: February 7, 2017
• Last Update Posted: March 18, 2020
• Sponsor: Philip Morris Products S.A.
• Information provided by (Responsible Party): Philip Morris Products S.A.

Tracking Information

• First Submitted Date: October 18, 2013
• First Posted Date: October 23, 2013
• Results First Submitted Date: February 5, 2016
• Results First Posted Date: February 7, 2017
• Last Update Posted Date: March 18, 2020
• Study Start Date: October 2013
• Actual Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 14, 2016)

• Maximum Concentration (Cmax) of Nicotine Following Single Use of mTHS 2.2, mCC and NNS [ Time Frame: 3 days ]
  Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares (geometric LS) means are provided.
• Area Under the Plasma Nicotine Concentration-Time Curve From Time Zero (Pre-product Use) to Last Time Point [AUC(0-last)] Following Single Use of mTHS 2.2, mCC and NNS [ Time Frame: 3 days ]
  Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares means are provided.

Original Primary Outcome Measures (submitted: October 22, 2013)

Nicotine maximum plasma concentration (Cmax) and area under the nicotine concentration-time curve from start of product use to time of last quantifiable concentration [AUC(0-last)] [ Time Frame: 1 day ]

To evaluate the rate and amount of nicotine absorption from THS 2.2 Menthol relative to mCC, following a single use of THS 2.2 Menthol and mCC

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Nicotine Pharmacokinetic Profile and Safety of the Tobacco Heating System 2.2 Menthol (THS 2.2 Menthol)
• Official Title: A Single-center, Open-label, Randomized, Controlled, Crossover Study to Investigate the Nicotine Pharmacokinetic Profile and Safety of Tobacco Heating System 2.2 Menthol (THS 2.2 Menthol) Following Single Use in Smoking, Healthy Subjects Compared to Menthol Conventional Cigarettes and Nicotine Nasal Spray
• Brief Summary: The primary objective of the study is to evaluate the pharmacokinetic (PK) profiles (rate and amount of nicotine absorbed) after a single use of the THS 2.2 Menthol (mTHS 2.2) compared to a single use of the menthol conventional cigarette (mCC) and nicotine nasal spray (NNS).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Smoking

Intervention

• Other: mTHS 2.2
  Single use of mTHS 2.2
• Other: mCC
  Single use of subject's own mCC
• Other: NNS
  Single administration of 1 mg of nicotine

Study Arms

• Active Comparator: mTHS 2.2 then mCC

  Each subject will follow the below study design:

  • Day 0 = Wash-out (1 day)
  • Day 1 = 1st intervention (single product use of mTHS 2.2)
  • Day 2 = wash-out
  • Day 3 = 2nd intervention (single product use of mCC).
  Interventions:

  • Other: mTHS 2.2
  • Other: mCC
• Active Comparator: mCC then mTHS 2.2

  Each subject will follow the below study design:

  • Day 0 = Wash-out (1 day)
  • Day 1 = 1st intervention (single product use of mCC)
  • Day 2 = wash-out
  • Day 3 = 2nd intervention (single product use of mTHS 2.2).
  Interventions:

  • Other: mTHS 2.2
  • Other: mCC
• Active Comparator: mTHS 2.2 then NNS

  Each subject will follow the below study design:

  • Day 0 = Wash-out (1 day)
  • Day 1 = 1st intervention (single product use of mTHS 2.2)
  • Day 2 = wash-out
  • Day 3 = 2nd intervention (single administration of NNS)
  Interventions:

  • Other: mTHS 2.2
  • Other: NNS
• Active Comparator: NNS then mTHS 2.2

  Each subject will follow the below study design:

  • Day 0 = Wash-out (1 day)
  • Day 1 = 1st intervention (single administration of NNS)
  • Day 2 = wash-out
  • Day 3 = 2nd intervention (single product use of mTHS 2.2).
  Interventions:

  • Other: mTHS 2.2
  • Other: NNS

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 14, 2016): 64
• Original Estimated Enrollment (submitted: October 22, 2013): 190
• Actual Study Completion Date: May 2014
• Actual Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subject is aged from 22 to 65 years (inclusive).
• Smoking, healthy subject as judged by the Investigator.
• Subject smoked at least 10 commercially available menthol CCs per day (with brand restrictions) over the last 4 weeks.
• Subject has smoked for at least the last 3 consecutive years.

Exclusion Criteria:

• As per Investigator judgment, the subject cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason).
• Subject has received medication within 14 days or within 5 half-lives of a drug (whichever is longer) which has an impact on CYP2A6 activity.
• Female subject is pregnant or breast feeding.
• Female subject does not agree to use an acceptable method of effective contraception.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 22 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01967719
• Other Study ID Numbers: ZRHM-PK-06-US; ZRHM-PK-06-US ( Other Identifier: Philip Morris Products S.A. )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Philip Morris Products S.A.
• Original Responsible Party: Same as current
• Current Study Sponsor: Philip Morris Products S.A.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Christelle Haziza, PhD; Philip Morris Products S.A.
• Principal Investigator: James L Borders, MD; Central Kentucky Research Associates

• PRS Account: Philip Morris Products S.A.
• Verification Date: March 2020