Clinical Trials Register

Summary
EudraCT Number:	2010-021788-33
Sponsor's Protocol Code Number:	A3051075
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-05-26
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2010-021788-33

A.3

Full title of the trial

A PHASE 4, MULTI-NATIONAL, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF VARENICLINE COMPARED TO PLACEBO FOR SMOKING CESSATION THROUGH REDUCTION

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study safety and effectiveness of a reduce to quit approach using varenicline versus placebo

A.3.2

Name or abbreviated title of the trial where available

Reduce to Quit

A.4.1

Sponsor's protocol code number

A3051075

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Pfizer Inc.235 East 42nd Street, New York, NY 10017 US
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Pfizer Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pfizer Inc
B.5.2	Functional name of contact point	Clinical Trials.gov Call Centre
B.5.3	Address:
B.5.3.1	Street Address	235 E 42nd Street
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	NY 10017
B.5.3.4	Country	United States
B.5.4	Telephone number	18007181021
B.5.5	Fax number	13037391119
B.5.6	E-mail	ClinicalTrials.govCallCentre@pfizer.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	CHAMPIX
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	VARENICLINE TARTRATE
D.3.9.1	CAS number	375815-87-5
D.3.9.3	Other descriptive name	VARENICLINE TARTRATE
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Smoking Cessation

E.1.1.1

Medical condition in easily understood language

Smokers

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Psychological processes [F02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10008374
E.1.2	Term	Cessation of smoking
E.1.2	System Organ Class	100000004869

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to compare the efficacy of varenicline to placebo for smoking cessation during the last 10 weeks of treatment in subjects who are not willing/able to make an abrupt quit attempt but are willing to reduce their smoking with the ultimate goal of quitting.

E.2.2

Secondary objectives of the trial

Secondary objectives are the comparison of varenicline to placebo during the last four weeks
of treatment and through the longer term follow-up phase to Week 52.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
2. Male and female cigarette smokers over the age of 18 years who are not willing/able to quit smoking within the next month but who are willing to attempt to reduce their smoking to work toward a quit attempt within the next 3 months.
3. Subjects must have smoked an average of at least 10 cigarettes per day during the past year and during the month prior to the screening visit, with no continuous period of abstinence greater than 3 months in the past year and who have an exhaled carbon monoxide (CO) >10 ppm at screening.
4. Subjects with history of lifetime or current mild to moderate (investigator opinion) major depressive disorder (MDD), depression, depressed mood, anxiety, and anxiety disorders (including general anxiety disorder (GAD), obsessive compulsive disorder (OCD) and phobias such as agoraphobia and social phobia) may be included if their condition is stable. Stability is defined as:
•If on medication, on the same dose for the past 6 months;
•No hospitalizations for exacerbations in the past 6 months.
5. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
6. Females who are not of childbearing potential (ie, who are surgically sterilized or at least 2 years postmenopausal) and who are not nursing may be included. Females who are of childbearing potential may be included provided that they are not pregnant, not nursing, and who meet all of the following criteria:
• Are instructed and agree to avoid pregnancy through 30 days after the last dose of study medication;
• Have a negative pregnancy test (beta-hCG) at Screening and Baseline and agree to use at least one of the birth control methods listed below:
• An oral contraceptive agent, an intrauterine device (IUD), an implantable contraception (eg, Norplant), or an injectable contraceptive (eg, Depo Provera) for at least 1 month prior to entering the study and will continue it's use through at least 30 days after the last dose of study medication; or:
• A double barrier method of contraception, (ie condom plus spermicide in combination with a female condom, diaphragm, cervical cap, or intrauterine device) or sexual abstinence prior to entering into the study and for at least least 30 days after the last dose of study drug

E.4

Principal exclusion criteria

1. Subjects with a history of a suicide attempt or any suicidal behavior in the past two years as assessed using the C-SSRS and/or the SBQ- R.
• History of suicidal ideation with intent/plan in the past 6 months (“yes” to Questions 4 and/or 5 on the C-SSRS) or at the screening or baseline visit.
2. Subjects with lifetime or current severe major depressive disorder (MDD), depression, depressed mood, anxiety, or anxiety disorder (including generalized anxiety disorder (GAD), obsessive compulsive disorder (OCD), and phobias such as agoraphobia and social phobia).
3. Subjects with unstable mild to moderate major depressive disorder (MDD), depression, depressed mood, anxiety, or anxiety disorder (including generalized anxiety disorder (GAD), obsessive compulsive disorder (OCD),and phobias) such as agoraphobia and social phobia
4. Subjects with a lifetime diagnosis or treatment for psychosis, panic disorder, bipolar disorder, post traumatic stress disorder (PTSD), or schizophrenia.
5. Subjects with alcohol or substance abuse or dependence (except nicotine) unless in full remission for at least 12 months.
6. Subjects with a positive urine drug screen (at screening or baseline) for drugs of abuse/potential abuse not prescribed for the treatment of a medical condition.
7. Subjects previously enrolled in a study that included varenicline (CP-526,555) or subject who have previously taken Chantix®/ Champix®. Subjects who have taken a very limited number of prescription doses may be considered pending discussion with the study clinician.
8. Subjects who have participated in other studies within 30 days prior to the screening visit of this study or any time during this study.
9. Subject with an SGOT (AST) or SGPT (ALT) greater than 3 times the upper limit of normal (ULN) or total bilirubin greater than 2 times the ULN at screening.
10. Subjects having clinically significant medical disorders or clinically significant laboratory test abnormalities as determined by the Principal Investigator.
11. Subjects with severe chronic obstructive pulmonary disease (COPD) defined as any subject who fulfills any of the following criteria:
• History of repeated exacerbations of COPD (greater than or equal to 3 in 3 years).
• Requires systemic corticosteroid maintenance (eg, oral prednisolone) for management of chronic symptoms.
• Is maintained on oxygen therapy for management of chronic symptoms.
12. Subjects with a recent (<5 years) history of cancer. Subjects with completely excised carcinoma in situ of the cervix or completely excised melanomas <5 years prior to screening may be considered pending discussion with the study clinician. Subjects with a remote (>5 years) history of cancer may be considered pending discussion with the study clinician.
• Subjects with cured basal cell or squamous cell carcinoma of the skin are allowed.
13. Subjects with evidence or history of clinically significant allergic reactions to drugs (eg, anaphylaxis or Stevens-Johnson syndrome).
14. Subjects with a clinically significant ECG at the screening visit (as determined by the Principal Investigator or medically appropriate designee).
15. Subjects with clinically significant cardiovascular disease in the past 2 months.
Examples of clinically significant cardiovascular disease include:
• Myocardial infarction;
• Coronary artery bypass graft (CABG);
• Percutaneous transluminal coronary angioplasty (PTCA);
• Severe or unstable angina;
• Serious arrhythmia;
• Clinically significant ECG conduction abnormalities;
• Heart failure.
16. Subjects with clinically significant cerebrovascular disease in the past 2 months.
Examples of clinically significant cerebrovascular disease include:
• Cerebrovascular accident (CVA), stroke;
• Documented transient ischemic attack (TIA).
17. Subjects taking a concomitant medication that is prohibited by this protocol
18. Subjects who do not agree to abstain from using non-cigarette tobacco products (including pipe tobacco, cigars, snuff, chewing tobacco, etc.) or marijuana during study participation.
19. Subjects who do not agree to abstain from using nicotine replacement therapy and other aids to smoking cessation during the treatment period.
20. Subjects who intend to donate blood or blood components while receiving study drug or within 1 month of the completion of the treatment phase of the study.
21. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

E.5 End points

E.5.1

Primary end point(s)

CO confirmed Continuous Abstinence (CA) during the last 10 weeks of treatment weeks 15-24.

E.5.1.1

Timepoint(s) of evaluation of this end point

CO confirmed CA during the last 10 weeks of treatment weeks 15-24

E.5.2

Secondary end point(s)

▪CO confirmed Continuous Abstinence (CA) Weeks 21-24;
▪CO confirmed Continuous Abstinence (CA) Weeks 21-52.
Other secondary endpoints:
▪7 day point prevalence of smoking cessation at Weeks 12, 24, and 52;
▪4 week point prevalence of smoking cessation at Week 52.

E.5.2.1

Timepoint(s) of evaluation of this end point

Key secondary: CO confirmed CA weeks 21-24 and also weeks 21-52. Other: 7 day point prevalence of smoking cessation at Weeks 12,24 and 52; 4 week point prevalence of smoking cessation at Week 52

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

Czech Republic

Egypt

Germany

Japan

Mexico

Taiwan

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1