Efficacy and Tolerability of Combination Varenicline With... | NCT04188106

NCT04188106

Status Module

Sponsor/Collaborators Module

Name	Class
Foundation for a Smoke Free World INC	OTHER

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Hydroxyzine and Varenicline	Experimental	Participants enrolled in the study will take the FDA approved starter kit of varenicline for the first week of medication administration (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7). During the first week, participants will also receive hydroxyzine dosed in a similar manner, 50 mg nightly for the first 3 days, then twice daily, 25 mg in the morning and 50 mg at night. After the first week, participants will receive the FDA-approved dose of varenicline (1 mg twice daily) combined with hydroxyzine, 25 mg in the morning and 50 mg at nighttime. All medications will be dosed orally.	Drug: Varenicline Pill Drug: Hydroxyzine Pill

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Varenicline Pill	Drug	FDA approved starter kit of varenicline (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7) followed by FDA-approved dose of varenicline (1 mg twice daily) for the remaining 11 weeks

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in 10-item Perceived Stress Scale (PSS-10) Following Smoking Cessation (While Taking Arenicline and Hydroxyzine).	Stress levels in the last 30 days will be measured using the 10-item Perceived Stress Scale (PSS-10). The PSS-10 uses a 5-point scale (0 - never, 1 = almost never, 2 = once in a while, 3 = often, 4 = very often). Total scores range from 0 to 40. Scores ranging from 0-13 would be considered low stress. Scores ranging from 14-26 would be considered moderate stress. Scores ranging from 27-40 would be considered high perceived stress.	Weeks 1, 2, 4, 8, 12
Changes in Anxiety Using the 6-item State-Trait Anxiety Inventory (STAI)	Trait and state anxiety levels will be monitored for changes using the 6-item State-Trait Anxiety Inventory (STAI). All items are rated on a 4-point scale ("1-Almost Never" to "4-Almost Always"). The range of scores is from 6 to 24. Higher scores indicate greater anxiety.	Weeks 1, 2, 4, 8, 12
Changes in Depression Using the Patient Health Questionnaire (PHQ-9)	Depression will be monitored for changes using the Patient Health Questionnaire (PHQ-9). The PHQ-9 uses a 4-point scale (Not at all = 0; Several days = 1;More than half the days = 2; Nearly every day = 3). The sum of the scores is calculated (Score range is 0 to 27): 1-4 Minimal depression 5-9 Mild depression 10-14 Moderate depression 15-19 Moderately severe depression 20-27 Severe depression	Weeks 1, 2, 4, 8, 12

Secondary Outcomes

Measure	Description	Time Frame
Effects of Varenicline on Self-reported Smoking Reduction Prior to the Quit Date	Previous research has shown that abstinence at the end of treatment is strongly predicted by the extent to which smokers spontaneously reduce ad libitum smoking in the initial weeks of pharmacotherapy that is initiated before the quit-smoking date. This measure will assess the extent of smoking reduction in participants during the initial seven days of treatment (prior to their planned quit date) - assessed via a self-report number of cigarettes per day. Data is recorded as a mean change.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has signed the consent form and is able to read and understand the information provided in the consent form.
Is 19 to 65 years of age (inclusive) at screening.
Smokes at least 10 commercially available cigarettes per day for the last 12 months.
Has an expired air carbon monoxide reading of at least 10 ppm at screening.
Express a desire to quit smoking within the next 30 days at screening.
Willing and able to comply with the requirements of the study.
Participant owns a smart phone with text message and data capabilities.

Exclusion Criteria:

Is unhealthy or cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason) as judged by the Investigator or designated medical staff based on all available assessments from the screening period (e.g., safety laboratory, vital signs, physical examination, ECG, concomitant medications and medical history).
PHQ-9 score greater than 9, or a score greater than 0 on item #9 ("Thoughts that you would be better off dead, or of hurting yourself in some way") at screening.
High blood pressure (systolic > 150 mmHg or diastolic >95 mmHg) at screening.
Body mass index (BMI) less than 15.0 kg/m2 or greater than 40.0 kg/m2.
Coronary heart disease, structural cardiac disease, cardiac dysrhythmias, abnormal ECG (e.g. prolonged QTc), syncope, cardiac chest pain, or history of heart attack or heart failure.
Has received psychotherapy or behavioral treatments potentially impacting symptoms of depression, anxiety, or nicotine withdrawal within 30 days of screening, or during the study.
Taking antidepressants, psychoactive medications (e.g. antipsychotics, benzodiazepines, hypnotics) or medications that prolong QTc.
Positive urine drug test for cocaine, marijuana, opiates, amphetamines or methamphetamines.
Use of smokeless tobacco (chewing tobacco, snuff), cigars, pipes, hookah, e-cigarettes, nicotine replacement therapy or other smoking cessation treatments within 14 days of enrollment.
Pregnant or nursing (by self-report) or has a positive pregnancy test.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Rose Research Center		Charlotte	North Carolina	28262	United States
Rose Research Center

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Hydroxyzine and Varenicline	Participants enrolled in the study will take the FDA approved starter kit of varenicline for the first week of medication administration (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7). During the first week, participants will also receive hydroxyzine dosed in a similar manner, 50 mg nightly for the first 3 days, then twice daily, 25 mg in the morning and 50 mg at night. After the first week, participants will receive the FDA-approved dose of varenicline (1 mg twice daily) combined with hydroxyzine, 25 mg in the morning, and 50 mg at nighttime. All medications will be dosed orally.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 4, 2019

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Hydroxyzine and Varenicline

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Hydroxyzine and Varenicline	Participants enrolled in the study will take the FDA approved starter kit of varenicline for the first week of medication administration (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7). During the first week, participants will also receive hydroxyzine dosed in a similar manner, 50 mg nightly for the first 3 days, then twice daily, 25 mg in the morning and 50 mg at night. After the first week, participants will receive the FDA-approved dose of varenicline (1 mg twice daily) combined with hydroxyzine, 25 mg in the morning and 50 mg at nighttime. All medications will be dosed orally. Varenicline Pill: FDA approved starter kit of varenicline (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7) followed by FDA-approved dose of varenicline (1 mg twice daily) for the remaining 11 weeks Hydroxyzine Pill: For the first week, participants will receive 50 mg nightly for the first 3 days, then twice daily, 25 mg in the morning and 50 mg at night for the remaining 12 weeks.

Units	Counts
Participants	BG00026

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000
Between 18 and 65 years	BG00026
>=65 years	BG000

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00042.115± 11.25

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00011
Male	BG00015

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000
Not Hispanic or Latino	BG00026

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001
Asian	BG0000

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00026

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in 10-item Perceived Stress Scale (PSS-10) Following Smoking Cessation (While Taking Arenicline and Hydroxyzine).

Stress levels in the last 30 days will be measured using the 10-item Perceived Stress Scale (PSS-10). The PSS-10 uses a 5-point scale (0 - never, 1 = almost never, 2 = once in a while, 3 = often, 4 = very often). Total scores range from 0 to 40.

Scores ranging from 0-13 would be considered low stress.
Scores ranging from 14-26 would be considered moderate stress.
Scores ranging from 27-40 would be considered high perceived stress.

The number of participants changes based on dropouts.

Posted

Mean

Standard Deviation

score on a scale

Weeks 1, 2, 4, 8, 12

ID	Title	Description
OG000	Hydroxyzine and Varenicline	Participants enrolled in the study will take the FDA approved starter kit of varenicline for the first week of medication administration (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7). During the first week, participants will also receive hydroxyzine dosed in a similar manner, 50 mg nightly for the first 3 days, then twice daily, 25 mg in the morning and 50 mg at night. After the first week, participants will receive the FDA-approved dose of varenicline (1 mg twice daily) combined with hydroxyzine, 25 mg in the morning, and 50 mg at nighttime. All medications will be dosed orally.

Units	Counts
Participants	OG00024

Title

Denominators

Categories

Change in PPS-10 from BL to Week 1

- ParticipantsOG00024

Title	Measurements
	OG000-1.38± 2.37

Change in PPS-10 from BL to Week 2

- ParticipantsOG000

Primary

Changes in Anxiety Using the 6-item State-Trait Anxiety Inventory (STAI)

Trait and state anxiety levels will be monitored for changes using the 6-item State-Trait Anxiety Inventory (STAI). All items are rated on a 4-point scale ("1-Almost Never" to "4-Almost Always"). The range of scores is from 6 to 24. Higher scores indicate greater anxiety.

The number of participants changes based on dropouts.

Posted

Mean

Standard Deviation

score on a scale

Weeks 1, 2, 4, 8, 12

ID	Title	Description
OG000	Hydroxyzine and Varenicline	Participants enrolled in the study will take the FDA approved starter kit of varenicline for the first week of medication administration (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7). During the first week, participants will also receive hydroxyzine dosed in a similar manner, 50 mg nightly for the first 3 days, then twice daily, 25 mg in the morning and 50 mg at night. After the first week, participants will receive the FDA-approved dose of varenicline (1 mg twice daily) combined with hydroxyzine, 25 mg in the morning, and 50 mg at nighttime. All medications will be dosed orally.

Units	Counts
Participants	OG000

Primary

Changes in Depression Using the Patient Health Questionnaire (PHQ-9)

Depression will be monitored for changes using the Patient Health Questionnaire (PHQ-9). The PHQ-9 uses a 4-point scale (Not at all = 0; Several days = 1;More than half the days = 2; Nearly every day = 3). The sum of the scores is calculated (Score range is 0 to 27):

1-4 Minimal depression
5-9 Mild depression
10-14 Moderate depression
15-19 Moderately severe depression
20-27 Severe depression

The number of participants changes based on dropouts.

Posted

Mean

Standard Deviation

score on a scale

Weeks 1, 2, 4, 8, 12

ID	Title	Description
OG000	Hydroxyzine and Varenicline	Participants enrolled in the study will take the FDA approved starter kit of varenicline for the first week of medication administration (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7). During the first week, participants will also receive hydroxyzine dosed in a similar manner, 50 mg nightly for the first 3 days, then twice daily, 25 mg in the morning and 50 mg at night. After the first week, participants will receive the FDA-approved dose of varenicline (1 mg twice daily) combined with hydroxyzine, 25 mg in the morning, and 50 mg at nighttime. All medications will be dosed orally.

Units	Counts
Participants

Secondary

Effects of Varenicline on Self-reported Smoking Reduction Prior to the Quit Date

Previous research has shown that abstinence at the end of treatment is strongly predicted by the extent to which smokers spontaneously reduce ad libitum smoking in the initial weeks of pharmacotherapy that is initiated before the quit-smoking date.

This measure will assess the extent of smoking reduction in participants during the initial seven days of treatment (prior to their planned quit date) - assessed via a self-report number of cigarettes per day. Data is recorded as a mean change.

The participants are divided as to whether they were successful in quitting smoking combustible cigarettes.

Posted

Mean

Standard Deviation

Cigs smoked per day

7 Days

ID	Title	Description
OG000	Hydroxyzine and Varenicline -- Successful in Quitting Smoking	Participants enrolled in the study will take the FDA-approved starter kit of varenicline for the first week of medication administration (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7). During the first week, participants will also receive hydroxyzine dosed in a similar manner, 50 mg nightly for the first 3 days, then twice daily, 25 mg in the morning and 50 mg at night. After the first week, participants will receive the FDA-approved dose of varenicline (1 mg twice daily) combined with hydroxyzine, 25 mg in the morning, and 50 mg at nighttime. All medications will be dosed orally.
OG001	Hydroxyzine and Varenicline -- Unsuccessful in Quitting Smoking

Secondary

Effects of Varenicline on Self-reported Smoking Reduction Prior to the Quit Date

This measure will assess the extent of smoking reduction in participants during the initial seven days of treatment (prior to their planned quit date) - assessed via expired air carbon monoxide (CO). Data is recorded as a mean change.

The participants are divided as to whether they were successful in quitting smoking combustible cigarettes.

Posted

Mean

Standard Deviation

CO in ppm

7 Days

ID	Title	Description
OG000	Hydroxyzine and Varenicline -- Successful in Quitting Smoking	Participants enrolled in the study will take the FDA-approved starter kit of varenicline for the first week of medication administration (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7). During the first week, participants will also receive hydroxyzine dosed in a similar manner, 50 mg nightly for the first 3 days, then twice daily, 25 mg in the morning and 50 mg at night. After the first week, participants will receive the FDA-approved dose of varenicline (1 mg twice daily) combined with hydroxyzine, 25 mg in the morning, and 50 mg at nighttime. All medications will be dosed orally.
OG001	Hydroxyzine and Varenicline -- Unsuccessful in Quitting Smoking

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Hydroxyzine and Varenicline	Participants enrolled in the study will take the FDA approved starter kit of varenicline for the first week of medication administration (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7). During the first week, participants will also receive hydroxyzine dosed in a similar manner, 50 mg nightly for the first 3 days, then twice daily, 25 mg in the morning and 50 mg at night. After the first week, participants will receive the FDA-approved dose of varenicline (1 mg twice daily) combined with hydroxyzine, 25 mg in the morning, and 50 mg at nighttime. All medications will be dosed orally.	0	26	0	26	21	26

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Hypersomnolence	Nervous system disorders	Systematic Assessment	EG00011 events9 affected26 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG00010 events10 affected26 at risk
Insomnia	Nervous system disorders	Systematic Assessment	EG0009 events9 affected26 at risk
Mood Changes	Psychiatric disorders	Systematic Assessment	EG0007 events7 affected26 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0005 events5 affected26 at risk
Elevated blood pressure	Cardiac disorders	Systematic Assessment	EG0004 events4 affected26 at risk
Vivid dreams	Nervous system disorders	Systematic Assessment	EG0004 events4 affected26 at risk

First MCP Posted Date

ID	Term
D016540	Smoking Cessation
D020447	Parasomnias
D009325	Nausea

Ancestor Terms

ID	Term
D015438	Health Behavior
D001519	Behavior
D012893	Sleep Wake Disorders
D009422	Nervous System Diseases
D001523	Mental Disorders
D012817	Signs and Symptoms, Digestive
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D000068580	Varenicline
D006919	Hydroxyzine

Ancestor Terms

ID	Term
D001552	Benzazepines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D011810	Quinoxalines
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring

Participants enrolled in the study will take the FDA-approved starter kit of varenicline for the first week of medication administration (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7). During the first week, participants will also receive hydroxyzine dosed in a similar manner, 50 mg nightly for the first 3 days, then twice daily, 25 mg in the morning and 50 mg at night. After the first week, participants will receive the FDA-approved dose of varenicline (1 mg twice daily) combined with hydroxyzine, 25 mg in the morning, and 50 mg at nighttime. All medications will be dosed orally.