A Study To Evaluate The Efficacy And Safety Of Vareniclin... | NCT01370356

NCT01370356

ID	Type	Description	Link
REDUCE TO QUIT

Status Module

Sponsor/Collaborators Module

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

Label	Type	Description	Intervention Names
Varenicline Tartrate	Active Comparator		Drug: Varenicline Tartrate
Placebo	Placebo Comparator		Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Varenicline Tartrate	Drug	Varenicline Tartrate oral tablets 2 (0.5mg) tablets twice a day for 24 weeks (first week titration)	Varenicline Tartrate

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Carbon Monoxide (CO) Confirmed 10-Week Continuous Abstinence (CA) From Smoking	Percentage of participants who remained abstinent from Week 15 to Week 24, inclusive, reporting no smoking and no use of nicotine-containing products since the last study visit or contact on the Nicotine Use Inventory (NUI) and confirmed by expired CO < 10 ppm at any time point (CO measurements conducted at the clinic visits) during Weeks 15 through 24, inclusive. Missing CO was imputed as negative (CO ≤ 10 ppm).	Week 15 - 24

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With CO Confirmed 4-Week CA From Smoking	Percentage of participants who remained abstinent from Week 21 to Week 24, inclusive, reporting no smoking and no use of nicotine-containing products since the last study visit or contact on the NUI and confirmed by expired CO < 10 ppm at any time point (CO measurements conducted at the clinic visits) during Weeks 21 through 24, inclusive. Missing CO was imputed as negative (CO ≤ 10 ppm).

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pharmacology Research Institute		Encino	California	91316	United States
Pharmacology Research Institute

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37142273	Derived	Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.
34611902	Derived	Hartmann-Boyce J, Theodoulou A, Farley A, Hajek P, Lycett D, Jones LL, Kudlek L, Heath L, Hajizadeh A, Schenkels M, Aveyard P. Interventions for preventing weight gain after smoking cessation. Cochrane Database Syst Rev. 2021 Oct 6;10(10):CD006219. doi: 10.1002/14651858.CD006219.pub4.

Label	URL
To obtain contact information for a study center near you, click here.	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Varenicline	Varenicline was titrated to the full dose during the first week (Day 1 - 3: 0.5 mg/day; Day 4 -7: 0.5 mg twice daily [BID]). From Week 2 to Week 24, the dose was 1 mg BID. Participants who had difficulties with tolerability were permitted to have the dose lowered temporarily or permanently to 0.5 mg BID. Data below are presented for the treated population.

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

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Varenicline	Varenicline was titrated to the full dose during the first week (Day 1 - 3: 0.5 mg/day; Day 4 -7: 0.5 mg BID). From Week 2 to Week 24, the dose was 1 mg BID. Participants who had difficulties with tolerability were permitted to have the dose lowered temporarily or permanently to 0.5 mg BID. One participant was assigned to varenicline as a male but is in fact female. Data below are presented for the treated population.
BG001	Placebo	Placebo was titrated and administered in the same manner as varenicline and reduction of dosing for difficulties with tolerability was also allowed. Data below are presented for the treated population.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG00032.1 OG0016.9

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Assuming true CA rate of 6.9% for placebo and 17.2% for varenicline (odds ratio ≥ 2.8), a study randomizing 1404 participants (1:1 ratio) has ≥90% power to detect a difference between the two groups. Analysis was done using a logistic regression model; treatment effect as explanatory variable and investigative center as covariate. The interaction effect was tested using an expanded logistic regression model including treatment-by-center interaction.	Regression, Logistic		<0.0001	Statistical test was 2-sided and a 0.05 level of significance was used. A fixed-sequence procedure was used to adjust for multiplicity. Hierarchy of comparisons: 1) 10-week CA for Weeks 15 - 24, 2) CA for Weeks 21 - 24, 3) CA for Weeks 21 - 52.	Odds Ratio (OR)	8.74			2-Sided	95	6.09	12.53

Secondary

Percentage of Participants With CO Confirmed 4-Week CA From Smoking

Percentage of participants who remained abstinent from Week 21 to Week 24, inclusive, reporting no smoking and no use of nicotine-containing products since the last study visit or contact on the NUI and confirmed by expired CO < 10 ppm at any time point (CO measurements conducted at the clinic visits) during Weeks 21 through 24, inclusive. Missing CO was imputed as negative (CO ≤ 10 ppm).

The Full Analysis Set was referred to as the ITT population and was defined as all randomized participants. The ITT population was the primary analysis set for the efficacy analyses in this study.

Posted

Number

percentage of participants

Week 21 - 24

ID	Title	Description
OG000	Varenicline	Varenicline was titrated to the full dose during the first week (Day 1 - 3: 0.5 mg/day; Day 4 -7: 0.5 mg BID). From Week 2 to Week 24, the dose was 1 mg BID. Participants who had difficulties with tolerability were permitted to have the dose lowered temporarily or permanently to 0.5 mg BID.
OG001	Placebo	Placebo was titrated and administered in the same manner as varenicline and reduction of dosing for difficulties with tolerability was also allowed.

Secondary

Percentage of Participants With CO Confirmed Long Term CA From Smoking

Percentage of participants who remained abstinent from Week 21 to Week 52, inclusive, reporting no smoking and no use of nicotine-containing products since the last study visit or contact on the NUI and confirmed by expired CO < 10 ppm at any time point (CO measurements conducted at the clinic visits) during Weeks 21 through 52, inclusive. Missing CO was imputed as negative (CO ≤ 10 ppm).

The Full Analysis Set was referred to as the ITT population and was defined as all randomized participants. The ITT population was the primary analysis set for the efficacy analyses in this study.

Posted

Number

percentage of participants

Weeks 21 - 52

ID	Title	Description
OG000	Varenicline	Varenicline was titrated to the full dose during the first week (Day 1 - 3: 0.5 mg/day; Day 4 -7: 0.5 mg BID). From Week 2 to Week 24, the dose was 1 mg BID. Participants who had difficulties with tolerability were permitted to have the dose lowered temporarily or permanently to 0.5 mg BID.
OG001	Placebo	Placebo was titrated and administered in the same manner as varenicline and reduction of dosing for difficulties with tolerability was also allowed.

Secondary

Percentage of Participants With 7-Day Point Prevalence of Smoking Cessation

The 7-day point prevalence of abstinence was defined as being abstinent from smoking and using tobacco products during the last 7 days at Week 12, 24, and 52. The participant's smoking status and other nicotine use was evaluated based on the "last 7 days" questions on the NUI and confirmed by CO expiration. Responders were defined as those, who answered "no" to both questions ("Has the subject smoked any cigarettes (even a puff) in the last 7 days?"; and "Has the subject used any nicotine products and/or other tobacco.... in the last 7 days?") and whose expired CO < 10 ppm. Missing CO was imputed as negative (CO ≤ 10 ppm).

The Full Analysis Set was referred to as the ITT population and was defined as all randomized participants. The ITT population was the primary analysis set for the efficacy analyses in this study.

Posted

Number

percentage of participants

Week 12, 24, and 52

ID	Title	Description
OG000	Varenicline	Varenicline was titrated to the full dose during the first week (Day 1 - 3: 0.5 mg/day; Day 4 -7: 0.5 mg BID). From Week 2 to Week 24, the dose was 1 mg BID. Participants who had difficulties with tolerability were permitted to have the dose lowered temporarily or permanently to 0.5 mg BID.
OG001	Placebo	Placebo was titrated and administered in the same manner as varenicline and reduction of dosing for difficulties with tolerability was also allowed.

Secondary

Percentage of Participants With 4-Week Point Prevalence of Smoking Cessation

The 4-week point prevalence of abstinence was defined as being abstinent from smoking and using tobacco products during the last 4 weeks of the study. The participant's smoking status and other nicotine use was evaluated based on the "last 4 weeks" questions on the NUI and confirmed by CO expiration. Responders were defined as those, who answered "no" to both questions ("Has the subject smoked any cigarettes (even a puff) in the last 4 weeks?"; and "Has the subject used any nicotine products and/or other tobacco.... in the last 4 weeks?") and whose expired CO < 10 ppm. Missing CO was imputed as negative (CO ≤ 10 ppm).

The Full Analysis Set was referred to as the ITT population and was defined as all randomized participants. The ITT population was the primary analysis set for the efficacy analyses in this study.

Posted

Number

percentage of participants

Week 52

ID	Title	Description
OG000	Varenicline	Varenicline was titrated to the full dose during the first week (Day 1 - 3: 0.5 mg/day; Day 4 -7: 0.5 mg BID). From Week 2 to Week 24, the dose was 1 mg BID. Participants who had difficulties with tolerability were permitted to have the dose lowered temporarily or permanently to 0.5 mg BID.
OG001	Placebo	Placebo was titrated and administered in the same manner as varenicline and reduction of dosing for difficulties with tolerability was also allowed.

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	Varenicline	Varenicline was titrated to the full dose during the first week (Day 1 - 3: 0.5 mg/day; Day 4 -7: 0.5 mg BID). From Week 2 to Week 24, the dose was 1 mg BID. Participants who had difficulties with tolerability were permitted to have the dose lowered temporarily or permanently to 0.5 mg BID.			28	751	467	751
EG001	Placebo	Placebo was titrated and administered in the same manner as varenicline and reduction of dosing for difficulties with tolerability was also allowed.			16	742	339	742

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Angina pectoris	Cardiac disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Myocardial infarction	Cardiac disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0012 affected742 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Gastritis	Gastrointestinal disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Ileus	Gastrointestinal disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Pancreatic cyst	Gastrointestinal disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Vomiting	Gastrointestinal disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Chest pain	General disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0011 affected742 at risk
Death	General disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Acute tonsillitis	Infections and infestations	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Cellulitis	Infections and infestations	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Laryngitis	Infections and infestations	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Lobar pneumonia	Infections and infestations	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Peritonitis	Infections and infestations	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Costochondritis	Musculoskeletal and connective tissue disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0011 affected742 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Bladder transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Epilepsy	Nervous system disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Intercostal neuralgia	Nervous system disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Migraine	Nervous system disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Presyncope	Nervous system disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Ruptured cerebral aneurysm	Nervous system disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Alcohol abuse	Psychiatric disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Alcoholism	Psychiatric disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Delirium tremens	Psychiatric disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Depression suicidal	Psychiatric disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Intentional self-injury	Psychiatric disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Suicidal ideation	Psychiatric disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Calculus ureteric	Renal and urinary disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0002 affected751 at risk EG0010 affected742 at risk
Ovarian haemorrhage	Reproductive system and breast disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk
Hospitalisation	Surgical and medical procedures	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Aortic aneurysm rupture	Vascular disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Hypertension	Vascular disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0011 affected742 at risk
Hypertensive crisis	Vascular disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0001 affected751 at risk EG0010 affected742 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA (v16.1)	Non-systematic Assessment	EG0000 affected751 at risk EG0011 affected742 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA (v16.1)	Non-systematic Assessment	EG00038 affected751 at risk EG00113 affected742 at risk
Nausea	Gastrointestinal disorders	MedDRA (v16.1)	Non-systematic Assessment	EG000209 affected751 at risk EG00167 affected742 at risk
Fatigue	General disorders	MedDRA (v16.1)	Non-systematic Assessment	EG00046 affected751 at risk EG00134 affected742 at risk
Irritability	General disorders	MedDRA (v16.1)	Non-systematic Assessment	EG00039 affected751 at risk EG00130 affected742 at risk
Nasopharyngitis	Infections and infestations	MedDRA (v16.1)	Non-systematic Assessment	EG00098 affected751 at risk EG00189 affected742 at risk
Upper respiratory tract infection	Investigations	MedDRA (v16.1)	Non-systematic Assessment	EG00063 affected751 at risk EG00163 affected742 at risk
Headache	Nervous system disorders	MedDRA (v16.1)	Non-systematic Assessment	EG00062 affected751 at risk EG00154 affected742 at risk
Abnormal dreams	Psychiatric disorders	MedDRA (v16.1)	Non-systematic Assessment	EG00086 affected751 at risk EG00143 affected742 at risk
Anxiety	Psychiatric disorders	MedDRA (v16.1)	Non-systematic Assessment	EG00052 affected751 at risk EG00165 affected742 at risk
Insomnia	Psychiatric disorders	MedDRA (v16.1)	Non-systematic Assessment	EG00080 affected751 at risk EG00151 affected742 at risk

Two cases of fetal exposure during pregnancy occurred but are not included in the SAE section as they did not meet the criteria of serious in the safety database. One of them relates to a non-study participant who was the study participant's partner.

Certain Agreements

ID	Term
D016540	Smoking Cessation
D000074264	Smoking Reduction

ID	Term
D000068580	Varenicline

ID	Term
D015438	Health Behavior
D001519	Behavior
D012907	Smoking

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