Cytisine for nicotine-containing electronic cigarette and tobacco cigarette cessation: a randomized placebo-controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University of Rzeszow

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Behavior and Behavior Mechanisms [F01]

Trial duration

2 Nov 2024 → ongoing

Decision date (initial)

2023-11-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the effectiveness of cytisine plus behavioural support compared to placebo plus behavioural support for cessation of single use of EC containing nicotine (electronic cigarettes, vaping) or dual use of EC containing nicotine and TC (tobacco cigarettes, smoking) in participants who are motivated to quit EC containing nicotine or dual use of EC containing nicotine and TC.
The study will compare biochemically verified continuous abstinence rates (i.e., vaping and smoking) for 26 weeks preceding the 30-week follow-up from the start of treatment between two groups of single users of EC or dual users (EC and TC) allocated to either:
1) Intervention arm: a 12-week course of 1.5 mg cytisine tablets plus behavioural support
2) Comparator arm: a 12-week course of placebo tablets (appearance is like cytisine tablets) plus behavioural support

Secondary objectives 1

1. To assess effectiveness of cytisine in reduction of nicotine consumption and tobacco smoking compared to placebo in participants who are motivated to quit EC containing nicotine or dual use of EC containing nicotine and TC. To assess safety of cytisine compared to placebo for cessation of single use of EC containing nicotine (vaping) or dual use of EC containing nicotine and TC (smoking) in participants who are motivated to quit EC containing nicotine or dual use of EC containing nicotine and TC.

Conditions and MedDRA coding

electronic cigarette cessation

Regulatory references

Plan to share IPD

No

IPD plan description

Not applicaable

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. age >18 at the time of screening visit
2. willing to use mobile application during the treatment period (with the option to opt out during the study)
3. provides a valid mobile phone number and a valid e-mail address
4. the written, aware of consent to participate in the study including the consent to participate in the screening, baseline and follow-up visit after the trial accomplishment
5. a daily access of the participant to a mobile phone
6. single EC users: currently using EC containing nicotine and using it daily or at least five days per week for at least 1 month prior to the screening visit, screening semi-quantitative urine cotinine positive for recent nicotine use who did not use tobacco in any form in the past 3 months (verified carbon monoxide [CO] concentration in the exhaled air ≤ 5 ppm at the time of screening). Here, we define EC as handheld devices that heat a liquid to produce an aerosol for inhalation (this excluded heated tobacco products)
7. dual EC and TC users: currently using EC containing nicotine and using it daily or at least five days per week for at least 1 month prior to the screening visit who also smoke at least one TC [factory-made cigarettes and/or roll-your-own cigarettes] per day plus CO in the exhaled air > 5 ppm, screening semi-quantitative urine cotinine positive test for recent nicotine use
8. willing to make a quit attempt using the study products (cytisine or placebo)
9. the ability and willigness to complete all study visits
10. acceptance of the study requirements and commitment to complete all study procedures
11. female subjects of childbearing potential must practice a highly effective method of birth control throughout the study. Contraceptive measures will be reviewed with patients during the informed consent process. Females applying hormonal contraception must agree to use additional barrier contraception. The following methods of birth control are considered highly effective: ▪ oral contraceptive (combined or progestogen only) administered for at least one monthly cycle prior to study drug administration; or ▪ implants of levonorgestrel inserted for at least 1 month prior to the study drug administration but not beyond the third successive year following insertion; or ▪ injectable progestogen administered for at least 1 month prior to study drug administration; or ▪ double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository); or ▪ an intrauterine device (IUD), inserted by a qualified physician, with published data showing that the highest expected failure rate is less than 1% per year; or ▪ estrogenic vaginal ring; or ▪ complete abstinence from intercourse; or ▪ percutaneous contraceptive patches.
12. fertile man must practice barrier contraception along with application to the intercourse partner methods applicable to women with childbearing potential (WOCBP) indicated above
13. willing to use mobile application during the treatment period (with the option to opt out during the study)
14. provides a valid mobile phone number and a valid e-mail address

Exclusion criteria 10

1. pregnancy (including planning to become pregnant during the treatment phase of the study and 2 weeks after the last dose of study medication)
2. women who are of childbearing potential and are likely to become pregnant during the medication phase and are not willing to use a reliable form of contraception
3. breastfeeding
4. currently use any smoking cessation medication, including the nicotine-containing products and cytisine within at screening
5. a known hypersensitivity to cytisine or to any of the excipients
6. hospitalization for any of the following medical conditions in the previous 3 months: myocardial infarct/severe angina, stroke, severe arrhythmia or another severe heartrelated condition
7. self-report diagnosis of pheochromocytoma, heart failure (IV NYHA), untreated active peptic ulcer/gastroesophageal reflux disorder, moderate/severe renal insufficiency, epilepsy or untreated hyperthyroidism, uncontrolled hypertension (systolic blood pressure > 160 mmHg, diastolic blood pressure > 100 mmHg)
8. diagnosis of any non-treated and unstable psychotic disorders, including schizophrenia; If any subject becomes psychotic during the study, they must be removed from treatment and/or additional study visits.
9. malignancy that has not been in complete remission for at least three years
10. current participation in other clinical trials or smoking cessation programs

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 9

1. Biochemically verified (negative urine cotinine and NNAL concentration) continuous EC containing nicotine and TC abstinence for 26 weeks preceding the 30-week follow-up (from 4 week to 30 week) post the start of treatment.
2. Continuous EC containing nicotine cessation will be defined as self-reporting having remained quit for 26 weeks preceding follow-up at 30-week from the start of treatment and
3. allowing for no more than 5 vaping occasions, whether it be one puff or many while still holding the device (when the device is put away or after 10 min. the occasion is over, whichever comes first), with the additional criterion of no slip-ups (not even a puff) in the last week, and return of a negative biochemical test (cotinine and NNAL).
4. Continuous TC cessation will be defined as self-reporting having remained quit for 26 weeks preceding follow-up at 30-week from the start of treatment (having smoked no more than five cigarettes in that time, i.e,. Russell standard) and return of a negative biochemical test.
5. Only participants self-reporting continuous abstinence at final follow-up will be biochemically verified.
6. A participant with urine concentration < 50 ng/mL and urine NNAL concentration < 10 pg/ml will be considered abstinent from EC containing nicotine and TC.
7. A participant who vapes EC not containing nicotine (0 mg/mL) will be considered abstinent.
8. Participants who will report abstinence but will be unable or unwilling to complete biochemical verification (urine cotinine) will be classified as using EC (treatment failure) for the primary outcome.
9. . Participants who will report abstinence but will be unable or unwilling to complete biochemical verification (urine cotinine and NNAL) will be classified as using EC and TC (treatment failure) for the primary outcome.

Secondary endpoints 8

1. Self-reported continuous EC containing nicotine abstinence defined as self-report of having vaped no EC containing nicotine allowing for no more than 5 vaping occasions, whether it be one puff or many while still holding the device (when the device is put away or after 10 min the occasion is over, whichever comes first), with the additional criterion of no slip-ups, not even a puff, in the last week for 26 weeks preceding follow-up at 30- week (from 4 week to 30 week) post the start of treatment
2. Self-reported continuous EC containing nicotine abstinence at 2-week, 4-week, and 12- week post the start of treatment
3. Self-reported continuous TC abstinence defined as self-report of having remained quit for 26 weeks preceding follow-up at 30-week from the start of treatment (having smoked no more than five cigarettes in that time, i.e., Russell standard)
4. Self-reported continuous TC abstinence at 2-week, 4-week, and 12-week post the start of treatment
5. Self-reported 7-day point prevalence abstinence defined as prevalence of abstinence (no TC, not a single vaping EC containing nicotine) during seven consecutive days immediately preceding 2-week, 4-week, 12-week, and 30-week interview
6. Biochemically verified (negative urine cotinine and NNAL concentration) 7-day point prevalence abstinence defined as prevalence of abstinence (no TC, not a single vaping EC containing nicotine) during seven consecutive days immediately preceding 30-week interview
7. Self-reported nicotine consumption from EC per day and week (strength and volume of eliquid/cartridge used per day) at 2-week, 4-week, 12-week, and 30-week post the start of treatment among those participants who continue EC using
8. The proportion of SAEs and AEs compared across cytisine and placebo groups

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University of Rzeszow

Sponsor organisation

University of Rzeszow

Address

Aleja Rejtana 16c

City

Rzeszow

Postcode

35-959

Country

Poland

Scientific contact point

Organisation

University of Rzeszow

Contact name

Prof. Piotr Tutka

Public contact point

Organisation

University of Rzeszow

Contact name

Prof. Piotr Tutka

Locations

1 EU/EEA country · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications