UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A randomised, controlled, multi-centre open-label study in healthy Japanese subjects to evaluate the effect on biomarkers of exposure of switching from a conventional combustible cigarette to the glo tobacco heating product.
Title of the study (Brief title)	A study to examine changes in exposure to cigarette smoke chemicals when a smoker switches to using a tobacco heating product.
Region	Japan

Condition
Condition	Cigarette smoking
Classification by specialty	Adult
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To quantitatively assess within-arm changes in biomarkers of exposure (BoE) and biomarkers of biological effect (BoBE) following a forced switch from a conventional cigarette (commercial cigarette) to a tobacco heating product or cessation.
Basic objectives2	Others
Basic objectives -Others	To assess differences between arms in BoE and BoBE following a switch from a conventional cigarette to a THP or cessation. To determine nicotine PK parameters.
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Not applicable

Assessment
Primary outcomes	Biomarkers of exposure (BoE): CO, TNeq, total NNAL, total NNN, 3-HPMA, HMPMA, S-PMA, MHBMA, CEMA, 4-ABP, o-Tol, 2-AN, 1-OHP, HEMA, AAMA and GAMA.
Key secondary outcomes	Biomarkers of Biological Effect (BoBE): 8-Epi-PGF2alpha Type III and white blood cell count. PK endpoints: tmax, Cmax and AUC0-last.

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	NO
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	No need to know

Intervention
No. of arms	6
Purpose of intervention	Educational,Counseling,Training
Type of intervention	Other
Interventions/Control_1	Regular cigarette smoking, for 5 days after 2 day baseline period.
Interventions/Control_2	Switch from regular cigarette smoking to developmental THP use for 5 days after 2 day baseline period.
Interventions/Control_3	Mentholated cigarette smoking, for 5 days after 2 day baseline period.
Interventions/Control_4	Switch from mentholated cigarette smoking to mentholated developmental THP use for 5 days after 2 day baseline period.
Interventions/Control_5	Switch from regular cigarette smoking to marketed THP use for 5 days after 2 day baseline period.
Interventions/Control_6	Abstain from use of any tobacco products for 5 days after 2 day baseline period.
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	23 years-old <
Age-upper limit	55 years-old >
Gender	Male and Female
Key inclusion criteria	1. Subjects will be males or females of Japanese origin and between 23 and 55 years of age, inclusive. 2. Subjects will have a body mass index (BMI) between 17.6 and 32.0 kg/m2, inclusive; a body weight exceeding 50 kg (males) or 40 kg (females) 3. Subjects will be in good health, as judged by the PI or designee based on medical history, physical examination, vital signs assessment, 12-lead ECG, clinical laboratory evaluations and lung function tests 4. Subjects will have given their written informed consent to participate in the study and will have agreed to abide by the study restrictions. 5. Subjects must demonstrate the ability to comprehend the Informed Consent Form (ICF), be able to communicate well with the PI or their appropriately qualified designee, understand and comply with the requirements of the study, and be judged suitable for the study in the opinion of the PI or their appropriately qualified designee. 6. Subjects will be regular smokers of factory-made cigarettes whose chosen brand is within the ISO tar bands 6 mg to 8 mg. 7. Subjects will have smoked their chosen brand for a minimum of 6 months and will have smoked for at least 3 consecutive years prior to Screening. 8. Subjects will typically smoke at least 10 and a maximum of 30 cigarettes per day and must have a urine cotinine level >200 ng/mL and an exhaled breath CO level >10 ppm at Screening.
Key exclusion criteria	1. Male subjects who do not agree, or whose partners of childbearing potential do not agree, to use a barrier method of contraception in addition to a second highly effective method of contraception used by their female partners or to refrain from donating sperm from Admission until the end of the safety Follow-up period. 2. Female subjects of childbearing potential who do not agree to use a highly effective method of birth control in conjunction with male barrier method contraception from the time of signing the ICF until the end of the safety Follow-up period. 3. Female subjects who are pregnant or breastfeeding. 4. Subjects who have an acute illness requiring treatment within 4 weeks prior to Admission. 5. Subjects who have regularly used any nicotine or tobacco product other than commercially manufactured filter cigarettes within 14 days of Screening. 6. Subjects who are self-reported non-inhalers. 7. Subjects who, prior to enrolment, are planning to quit smoking in the next 12 months. 8. Subjects who have serum hepatitis; are carriers of HBsAg; are carriers of the hepatitis C antibody; have a positive result for the test for HIV antibodies; or have syphilis. 9. Subjects who have used prescription or OTC bronchodilator medication to treat a chronic condition within the 12 months prior to Admission. 10. Subjects who have any clinically relevant abnormal findings on the physical examination, medical history, ECG, lung function tests or clinical laboratory panel. 11. Subjects who have, or who have a history of, any clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatric, respiratory, metabolic, endocrine, haematological or other major disorder that, in the opinion of the PI, would jeopardise the safety of the subject or impact on the validity of the study results. 12. Subjects who have previously been diagnosed with any form of malignancy.
Target sample size	180

Research contact person
Name of lead principal investigator	Yoshihara Tatsuya
Organization	Fukuoka Mirai Hospital
Division name	Clinical Research Centre
Address	3-5-1, Kashiiteruha, Higashi-ku, Fukuoka
TEL	092-662-3608
Email	tatsuya-yoshihara@lta-med.com

Public contact
Name of contact person	Ian Fearon
Organization	British American Tobacco (Investments) Limited
Division name	Clinical Research
Address	Regents Park Road, Southampton, SO15 8TL, U.K.
TEL	4402380588641
Homepage URL
Email	ian_fearon@bat.com

Sponsor
Institute	British American Tobacco (Investments) Limited
Institute
Department

Funding Source
Organization	British American Tobacco (Investments) Limited Research and Development
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	British

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2016 Year 11 Month 24 Day

Progress
Recruitment status	No longer recruiting
Date of protocol fixation	2016 Year 11 Month 18 Day
Anticipated trial start date	2017 Year 01 Month 20 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2016 Year 11 Month 24 Day
Last modified on	2017 Year 05 Month 26 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000028686