A randomised, controlled, two-Centre open-label study in healthy Japanese subjects to evaluate the effect on biomarkers of exposure of switching from a conventional cigarette to a tobacco heating product

In total, 180 male or female smokers will be enrolled in this study. Smokers whose current brand of cigarettes is mentholated or non-mentholated will be enrolled, with the former being randomised only into the menthol product use or cessation groups, and the latter only into the non-menthol product use or cessation groups. Subjects of each gender will have a quota applied to ensure that they represent at least 40% of the total population and/or of each group. Ongoing monitoring of recruitment logs by the clinical sites will be performed to ensure that the gender split in the groups matches the protocol requirements.

Participants will be recruited into the study through advertisements on the clinic’s own website and local advertising that will not refer to the characteristics of the study products. Adult, healthy participants of either sex and of Japanese origin will be enrolled.

The suitability of participants who give informed consent will be assessed according to the inclusion criteria within 35 days before entering the study and verified upon arrival at the clinic for the in-clinic evaluation period. The universal inclusion criteria are current smokers (as verified at screening and admission using a urinary cotinine test (cotinine >200 ng/mL) and exhaled breath carbon monoxide (CO) test (CO >10 ppm)) who report typically smoking at least 10 and a maximum of 30 commercially available cigarettes per day, within the ISO tar bands of 6 mg to 8 mg; at least 3 years’ consecutive smoking history including smoking their preferred brand of cigarettes for at least 6 months immediately prior to screening; age between 23 and 55 years inclusive; weight of at least 50 kg (men) or 40 kg (women) and body mass index (BMI) between 17.6 and 32.0 kg/m², inclusive; no clinically-relevant abnormal findings on physical examination, vital signs assessment, ECG, clinical laboratory testing or lung function tests, or in the medical history, as judged by the investigators; the ability to communicate well with the investigators and understand and comply with the requirements of the study; willingness to refrain from consuming alcohol within 72 h before screening and the in-clinic evaluation; willingness to refrain from consuming and avoid being in the presence of the cooking of cruciferous vegetables and grilled, fried or barbequed food for 48 h before the first day of the in-clinic evaluation; willingness to avoid eating foods containing poppy seeds for 72 h prior to screening and the in-clinic evaluation; if of non-childbearing potential provide confirmation; if of childbearing potential subjects must not be pregnant or breastfeeding and must be using an acceptable method of contraception from from the time of signing the ICF until the end of the safety follow-up period; or being postmenopausal with amenorrhea for at least 1 year.

Additional inclusion criteria are; willing to use the study products (comparator cigarette or THP) and smoke only the products provided to them during clinical confinement, or to abstain from smoking if assigned to the cessation group.

Exclusion criteria may be applied at screening or at any time during the study. The universal exclusion criteria are male subjects who do not agree, or whose partners of childbearing potential do not agree, to use a barrier method of contraception (i.e., a condom with spermicide) in addition to a second highly effective method of contraception used by their female partners or to refrain from donating sperm from admission (Day −1) until the end of the safety follow-up period (5–7 days after discharge); 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 (i.e. a condom with spermicide) from the time of signing the ICF until the end of the safety follow-up period (5–7 days after discharge); female subjects who are pregnant or breastfeeding (this will be confirmed at screening and admission and any female subject who becomes pregnant during this study will be withdrawn); subjects who have donated ≥400 mL of blood within 12 weeks (males) or 16 weeks (females) prior to admission, plasma in the 2 weeks prior to admission or platelets in the 6 weeks prior to admission; subjects who have had an acute illness (e.g. upper respiratory tract infection, viral infection, etc.) requiring treatment within 4 weeks prior to admission; subjects who have regularly used any nicotine or tobacco product other than factory-made filter cigarettes within 14 days of screening; subjects who are self-reported or observed at admission by the clinic staff as non-inhalers (smokers who draw smoke from the cigarette into the mouth and throat but who do not inhale); subjects who have a significant history of alcoholism or drug/chemical abuse within 24 months prior to screening, as determined by the PI; subjects who have a positive urine drugs of abuse screen or alcohol breath test (either confirmed by repeat) at screening or admission; subjects who have serum hepatitis, are carriers of the hepatitis B surface antigen (HBsAg), are carriers of the hepatitis C antibody or have a positive result for the test for human immunodeficiency virus (HIV) antibodies, or have syphilis; subjects who have used prescription or over-the-counter (OTC) bronchodilator medication (e.g. inhaled or oral β-adrenergic agonists) to treat a chronic condition within the 12 months prior to admission; subjects who have received any medications or substances (other than tobacco) which interfere with the cyclooxygenase pathway (e.g. anti-inflammatory drugs including aspirin and ibuprofen) within 14 days prior to admission or which are known to be strong inducers or inhibitors of cytochrome P450 (CYP) enzymes within 14 days or 5 half-lives of the drug (whichever is longer) prior to admission; subjects who perform strenuous physical activity (exceeding the subject’s normal activity levels) within 7 days prior to screening or admission; subjects who are unable to communicate effectively with the PI/study staff (i.e. language problem, poor mental development, or impaired cerebral function); subjects who are unwilling or unable to comply with the study requirements; employees and immediate relatives of those employed in the tobacco industry or the clinical site; subjects who are still participating in another clinical study (e.g. attending follow-up visits) or who have participated in a clinical study involving administration of an investigational drug (new chemical entity) in the past 3 months prior to first product use; subjects who have any clinically relevant abnormal findings on the physical examination, medical history, ECG, lung function tests (forced expiratory volume after 1 s [FEV₁]/forced vital capacity [FVC] <0.7 at post-bronchodilator spirometry, post-bronchodilator FEV₁ < 80% predicted value, and post-bronchodilator FVC <80% predicted value) or clinical laboratory panel, unless deemed not clinically significant by the PI or their appropriately qualified designee; 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 or their appropriately qualified designee, would jeopardise the safety of the subject or impact on the validity of the study results; subjects who have previously been diagnosed with any form of malignancy; subjects who have any clinically significant abnormal laboratory safety findings at screening and prior to first product use, as determined by the PI (1 repeat assessment is acceptable); subjects who have previously taken part in or withdrawn from this study; and subjects who, in the opinion of the PI, should not participate in this study.

One further exclusion criterion is that subjects will be excluded from study participation if, prior to enrolment, they are planning to quit smoking in the next 12 months. All subjects will be informed that they are free to quit smoking and withdraw from the study at any time. Any subject who decides to quit smoking will be directed to appropriate stop smoking services.

All subjects will be reminded of the harms associated with smoking prior to enrolment onto the study and that they are free to voluntarily quit smoking and/or withdraw from the study at any time. If they do so, they will receive a pro-rata stipend. Investigators may also at any time withdraw a participant from the study if they deem this action to be in his or her best interest or that of other participants. The end-of-study examination will be undertaken when a participant leaves the study, if he or she agrees, and reasons for withdrawal will be recorded. If a subject cannot be assessed because he or she cannot be contacted after non-attendance of a scheduled event, they will be reported as lost to follow-up.

Subjects may be withdrawn from the study prematurely for the following reasons: if a subject experiences an intolerable adverse event (premature discontinuation will be at the discretion of either the PI or the subject, independent of the relationship of the AE to the study test product); if a subject develops a non-fulfilment of inclusion/exclusion criteria or concurrent disease, which at the discretion of the PI, no longer justifies the subject’s participation in this study; or if any deviations occur during the conduct of the study- this may include the subject’s erroneous inclusion in the study. Any protocol deviations detected during the study will be corrected when possible and the subject will be allowed to continue. All protocol deviations will be fully documented and considered for their effect on study objectives. Deviations that could lead to subject discontinuation from the study include: deviations which could affect subject’s safety (e.g. illness requiring treatment[s]) which in the clinical judgement of the PI (or after discussion with the Medical Monitor) might invalidate the study by interfering with the allocated test product or the willingness of the subject to comply with the study activities; deviations involving the use of any nicotine/tobacco products other than the intended conventional cigarettes or THPs; or deviations involving the use of any nicotine/tobacco products by the cessation group during the exposure period. A subject may also be withdrawn from the study: if the subject is uncooperative, including non-attendance (in these cases, efforts should be made by the PI to ascertain the reason and to ensure subject’s attendance as soon as possible); due to pregnancy; due to premature cancellation of the study; or at the subject’s personal request: the subject could decide, at any moment of the study, to stop his/her participation. The PI should ensure this is not due to AEs, in which case, this reason should be documented. Subjects do not have to provide a reason for withdrawing from the study if they do not wish to do so. Although withdrawals or dropouts are not expected to be replaced, the Sponsor will consider replacing participants to maintain the power of the study.

Separate randomisations will be provided for each site and each site will need to recruit 15 subjects for each arm. In total 3 randomisation lists will be produced. Arms A and B will be studied first so the first 60 subjects will be randomised to these two arms. Male subjects will be assigned starting at subject number 0001 onwards and female subjects will be assigned starting at subject number 0060 downwards. The remaining 2 lists will be produced for arms E and F (non-menthol users) and for arms C and D (menthol users). In each list 60 subjects will be randomised so that 30 subjects are assigned to each arm. Male subjects will be assigned starting at subject numbers 0061 and 0121 onwards in each list respectively and female subjects will be assigned starting at subject numbers 0120 and 0180 downwards in each list respectively. A suitably qualified person will monitor the randomisation to ensure there is at least 40% of each gender in an arm.

The randomisation will be performed by Covance and the clinics will enrol the participants and assign them to interventions. A suitably qualified person will monitor the randomisation to ensure there is at least 40% of each gender in an arm.

The study will be conducted under clinical confinement and subjects will not be allowed to bring their own cigarettes/THPs into the clinic. To ensure product use compliance in the clinic, all products will be used by subjects under the supervision of suitably qualified staff. Study products will be dispensed by clinic staff each time a study subject wishes to smoke a cigarette or use a THP. Records will be kept of all product usage and these records will be checked by the Clinical Research Associates (CRAs). Subjects in the cessation arm will neither be provided with cigarettes/THPs nor be allowed to enter the smoking rooms. Subjects randomised to one of the THP groups will receive training by clinic staff on how to operate their assigned THP device. The THPs will be charged and assembled for the subjects, who will only be required to activate the devices. Product information sheets will be provided for each of the THP test products.

Subjects will undergo telephone screening within 34 days prior to the first product use. Staff will verbally confirm that the subjects comply with the inclusion/exclusion criteria prior to attending the site for a screening visit.

Following the telephone screening and prior to first product use, subjects will attend a screening visit at one of the clinical sites. Prior to the screening visit, subjects will refrain from strenuous physical activity (exceeding the subject’s normal activity levels) for 7 days and abstain from alcohol for 72 h. Subjects will be asked to sign the study-specific ICF in the presence of a suitably trained clinical site clinical operations staff member prior to any screening procedures being performed. The information recorded for all subjects, regardless of their suitability for the study, will be retained and archived in accordance with the PI’s data retention policies.

Subjects will be asked to provide a urine sample for a cotinine screen to ensure that they are currently using nicotine-delivering products. Subjects will also be asked to provide an exhaled breath sample for a CO test to ensure that they smoke combustible cigarettes. They will only be enrolled into the study if their urine cotinine level is greater than 200 ng/mL and their exhaled breath CO level is greater than 10 ppm.

The following information and procedures will also be recorded and performed as part of the screening assessments: medical history; gender, race/ethnic origin, age, height, weight and BMI; vital signs, including supine blood pressure, supine pulse rate, respiratory rate, and axillary body temperature; resting 12-lead ECG; physical examination (may be performed at admission); lung function tests; urine drugs of abuse screen and alcohol breath test; clinical laboratory evaluations; hormone panel analysis (female subjects only); and nicotine use assessment (including tobacco and nicotine use history and Fagerström test for cigarette dependence (FTCD) questionnaire). All subjects will be given a demonstration of the THP products at screening.

Subjects will be advised to refrain from consuming cruciferous vegetables, and grilled, smoked, fried or barbequed food for 48 h prior to admission. This will also include being in the presence of the cooking of cruciferous vegetables, and grilled, smoked, fried or barbequed food. Subjects will be asked to confirm this as part of the clinic admission procedure on Day −1.

Subjects will be advised that they must not eat food containing poppy seeds for 3 days before both screening and admission (Day −1), as consumption of poppy seeds can lead to a positive opiate result in the drugs of abuse test.

Subjects will be instructed to refrain from consuming alcohol for 72 h prior to admission (Day −1) and will be requested not to undertake vigorous exercise outside of their usual routine from 7 days before Admission (Day −1) until after the post-study assessments.

Female subjects participating in the study who are of non-childbearing potential will not be required to use contraception. Women of non-childbearing potential are defined as permanently sterile (i.e. due to hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or confirmed tubal occlusion) or postmenopausal (defined as at least 12 months post-cessation of menses without an alternative medical cause). Postmenopausal status will be confirmed with a screening serum follicle-stimulating hormone (FSH) level greater than 40 mIU/mL.

Female subjects of childbearing potential will be required to follow contraception requirements from the time of signing the ICF until the end of the safety follow-up period (5–7 days after discharge). Male subjects and their partners of childbearing potential will be required to follow contraception requirements from admission (Day −1) until the end of the safety follow-up period (5–7 days after discharge).

Women of childbearing potential should be using one of the following acceptable methods of contraception: combined (oestrogen and progestogen containing) oral, intravaginal or transdermal hormonal contraception associated with inhibition of ovulation; progestogen-only hormonal contraception, either oral, injected or implanted, associated with inhibition of ovulation; progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary mode of action; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; male or female condom with spermicide; cap, diaphragm or sponge with spermicide.

Subjects who practice true abstinence, which must be due to the subject’s lifestyle choice; i.e. the subject should not become abstinent just for the purpose of study participation, are exempt from contraceptive requirements. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

For male subjects, sexual intercourse with female partners who are pregnant or breastfeeding should be avoided unless condoms are used, from admission (Day −1) until the end of the safety follow-up period (5–7 days after discharge). Male subjects are required to refrain from donation of sperm from admission (Day −1) until the end of the safety follow-up period (5–7 days after discharge).

For subjects who are exclusively in same sex relationships, contraceptive requirements will not apply.

From admission until discharge, the only permitted nicotine intake will be from subjects’ assigned study products (cigarette or THP). Subjects randomised to the cessation group (Group F) will be instructed to abstain from all product use after the baseline period until they are discharged at the end of Day 7. Subjects for the pharmacokinetic assessment (Groups A to E) will be instructed to abstain from use of any nicotine-containing products for a minimum of 12 h prior to the pharmacokinetic assessment after which a single product use session will occur.

The baseline period will begin at admission on the afternoon of Day −1 and will end on the evening of Day 2 (Table 3). At admission, it will be confirmed that the subject continues to meet all of the study inclusion/exclusion criteria. Any subject who is eligible at screening, but who fails to meet the criteria at admission will be considered a screening failure and will be replaced. Subjects who do not fulfil the entry criteria prior to enrolment, but who are considered eligible, will be immediately withdrawn from the study when the non-fulfilment is detected. If the subject has not yet been enrolled into the study, they can be replaced.

Any changes in medical history since last visit will be discussed with the subject (including intake of any excluded medications) and documented. Subjects will be required to give any tobacco or nicotine products that they have with them to the clinic staff upon admission (these will be returned at the end of the study).

Subjects will be excluded from the study if they have used any nicotine or tobacco product other than commercially manufactured filter cigarettes within 14 days of screening. Only subjects willing to smoke only the cigarettes or THP distributed by the clinical site staff during the in-clinic evaluation period will be enrolled into the study. Subjects will be instructed on how to request their assigned product and return the extinguished cigarette/THP.

The exposure period will begin on the evening of day 2 and will continue until the evening of day 7 (Table 4). The subjects will be switched to their assigned product (conventional cigarette, assigned THP or cessation) on the evening of day 2 after completion of the 24-h urine collection. All subjects undergo the same procedures with the exception of the cessation group, Group F, who will not be allowed to use any products during the exposure period.

The nicotine pharmacokinetic assessment period will be from collection of the final 24-h urine sample on Day 7 until discharge on the afternoon of Day 8 (Table 5). All subjects in Groups A to E will remain in the clinic for the pharmacokinetic assessment period. These subjects will undertake a minimum 12-h period of smoking abstinence before being asked to use the cigarette or THP assigned to them during the exposure phase in a single-use session. Subjects will not consume food for a minimum of 1 h before the start of the pharmacokinetic assessment period until the end of the pharmacokinetic assessment period.

Subjects will be discharged from the clinical site following their final 24-h urine collection on Day 7 (Group F) or after their last pharmacokinetic assessment on Day 8 (Groups A-E). The PI will check on all subjects’ wellbeing prior to discharge and provide cessation advice. If necessary, subjects will remain at the clinical site until any AEs of concern have resolved. Discharge assessments will include adverse events, vital signs, physical examination (abbreviated), ECG, lung function test, clinical laboratory assessments and pregnancy test (women of childbearing potential only). Subjects in all groups, should they wish to continue smoking after the study, will be advised to smoke their first post-study cigarette prior to leaving the clinical site to allow management of any potential adverse events.

The follow-up assessment will be performed by a phone call to the subjects between 5 and 7 days after discharge. The PI will obtain information on any new AEs and new/changes to concomitant medication since discharge and complete the corresponding pages of the eCRF. Provided there are no AEs which require further attention, the subject’s participation in the study will be complete. A visit will be scheduled if deemed necessary by the PI or their suitably qualified designee.

Subjects who, after randomisation, discontinue the trial prematurely should be encouraged to participate in this follow-up procedure. If their withdrawal is due to safety evaluations, then the subjects will be followed until these return to baseline levels or until the PI has determined that these events are no longer clinically significant.

Subjects who develop an AE at any time during the study will be followed until any required evaluations have returned to baseline or until the PI has determined that these events are no longer clinically significant. Reported AEs will be followed until resolution whenever possible.

If, in the opinion of the PI, the clinical observations in the study suggest that it may be unwise to continue, the PI may terminate part of or the entire study after consultation with the Sponsor. In addition, the Sponsor may terminate part of or the entire study for safety or administrative reasons. A written statement fully documenting the reasons for study termination will be provided to the IRB.

Socio-demographic data (sex, age) will be recorded at screening.

Subjects will be asked about their smoking history at screening. This will include questions to evaluate whether the subject has smoked for at least the last 3 consecutive years, to determine the number of cigarettes smoked by the subject per day on average, to check that the subject has smoked their chosen brand of conventional cigarette consistently for at least 6 months, and to determine if the subject regularly uses any nicotine or tobacco product other than commercially manufactured filter cigarettes. In addition, the subject will be asked if he/she is planning to quit smoking within the next 12 months. A colour photocopy of the subjects preferred cigarette pack, including the surface showing tar/nicotine content, will be taken.

Relevant medical history, as determined by the PI or their suitably qualified designee, will be documented at screening and admission. Medical history will include any clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatric, respiratory, metabolic, endocrine, haematological or other major disorders. Medical history is defined as any condition that started and ended prior to screening. A concomitant disease is any disease that started prior to, and which was still ongoing, at screening.

Prior medications taken within 28 days prior to screening and any concomitant medication will be documented at screening and admission. Any medication which was started prior to screening and is still being taken by the subject, or any medication started after screening, will be considered to be a concomitant medication. This includes both prescription and OTC products.

Details of prior and concomitant medications to be recorded include the drug name (generic and trade name if applicable), route of administration, total dose/unit, indication, start date and stop date.

Blood and urine samples will be collected for clinical laboratory evaluations at screening, admission, and discharge (see Table 6 for details). Additional clinical laboratory evaluations will be performed at other times if judged to be clinically appropriate or if the ongoing review of the data suggests a more detailed assessment of clinical laboratory safety evaluations is required. The PI will perform a clinical assessment of all clinical laboratory data.

Urine samples will be collected over consecutive 24-h time periods, beginning on the evening (between approx. 19:00 and 20:00) of admission (Day −1), with the last time period finishing on the evening (between approx. 19:00 and 20:00) on Day 7. All urine voided will be collected. The samples will be refrigerated at between 2 °C to 8 °C.

The urine samples collected during a single 24-h interval will be pooled together at the end of the 24-h period and weighed. The samples will be related to the day on which the 24-h collection period ended. The pooled samples will be thoroughly mixed before providing aliquots for analyses. The total volume of all urine collected over each 24-h period will be calculated from weight and specific weight. Urine aliquots will be stored in suitably labelled tubes at −18 °C to −25 °C pending assay.

The urinary BoE and BoBE that will be analysed are presented in Table 1. Creatinine in urine will also be calculated and used to report BoBE as amount per unit of creatinine. The independent laboratories performing the analysis of BoE and BoBE will be blind to each subject’s test product allocation.

Blood samples for white blood cell count will be collected in 2 appropriately sized EDTA tubes at approximately 16:00 on Day 2, Day 5 and Day 7 using direct venepuncture.

Subjects in Groups A to E will be required to abstain from using any nicotine products from the evening of Day 7 (after the last 24 h urine sample), until the morning of Day 8 (at least 12 h of smoking cessation). Subjects will then be required to smoke either 1 conventional cigarette or use THP with 1 tobacco stick for up to 5 min, dependent on their study group. Blood samples (13 × 4 mL) will be taken by direct venepuncture or from a cannula placed in a forearm vein, at 5 (±2) minutes before smoking, and at 1 (±0.5), 3 (±0.5), 4 (±0.5), 5 (±0.5), 6 (±0.5), 7 (±0.5), 10 (±1), 15 (±1), 30 (±5), 60 (±5), 120 (±10), and 240 (±10) minutes relative to first puff. The concentration of nicotine will be measured in all plasma samples.

During the single product use in the pharmacokinetic assessment period (Day 8), the number of individual puffs taken by the subject on either a conventional cigarette or on the assigned THP product will be recorded by the clinical site staff in the eCRF.

Exhaled carbon monoxide (eCO) levels will be measured at Screening, Admission and at the same time each evening (between approx. 16:30 and 17:30) from Day 1 to Day 7. The date and time of the CO measurement along with the eCO in parts per million will be recorded on the source documents and entered on the eCRF. Each eCO measurement will take place a minimum of 30 min after the subject’s previous use of any tobacco product.

Spirometry with and without a short-acting bronchodilator (sultanol) will be conducted at screening, admission and discharge/early termination to evaluate inclusion/exclusion criteria (the post-bronchodilator results). At screening, spirometry without bronchodilator will be conducted first, followed by spirometry with bronchodilator. Also at screening, spirometry will be conducted at least 1 h after smoking. Spirometry will be used to measure forced vital capacity (FVC), forced expiratory flow 25–75% (FEF_25–75%), peak flow, and forced expiratory volume in 1 s (FEV₁).

Spirometry will be conducted using the guidelines specified by the Third National Health and Nutrition Examination Survey (NHANES III; [10]). Spirometry testing will be performed in accordance with procedures of the American Thoracic Society/European Respiratory Society [21]. Predicted FEV₁ and FVC will be calculated according to the formula recommended by the Japanese Respiratory Society.

Measurements will be repeated if there are technical issues during testing or if the subject shows signs of fatigue. Measurements will not be repeated if the results fall under the levels required for enrolment in the study. If a subject shows signs of fatigue during repeated testing, testing will be halted to ensure that the subject does not become exhausted and will only be recommenced at the physician’s discretion. No more than 8 manoeuvers will be performed. The spirometry traces will be copied and inserted into the source documents. The spirometer will be kept calibrated as recommended by the manufacturer.

The number of conventional cigarettes smoked or THP sticks used will be recorded over continuous 24-h periods (concurrent with urine collection periods) from the evening of Day −1 until the beginning of the exposure period (Group F) or the evening of Day 7 (Groups A to E).

Potential nicotine dependence will be assessed via a questionnaire at Screening using a FTCD questionnaire in its revised version ([6]; Table 8). The questionnaire consists of 6 questions which will be answered by the subject himself/herself. The scores obtained on the test permit the classification of nicotine dependence into 3 levels: Mild (0–3 points), moderate (4–6 points), and severe (7–10 points).

A product satisfaction question will be administered to subjects during the pharmacokinetic assessment period (Day 8) between the 10-min and 15-min blood draws. The question, “Can you tell me how much do you like this tobacco product?”, will be answered by the subject himself/herself. The subject will provide responses on a 7-point Likert scale ranging from “1 – I dislike it a lot” to “7 – I like it a lot” (scores of 2–6 will not have a descriptor).