To Assess the Bioequivalence of the 4mg Prototype Mini Nicotine Lozenge to the Reference Product (Nicorette) in Healthy Smokers

NCT03543137 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 207790
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the bioequivalence of the test product (Nicotine Prototype Mini lozenge 4 milligrams \[mg\]) to a commercial reference product (nicotine polacrilex mini lozenge 4mg) in healthy smokers under fasting conditions.

Conditions

Tobacco Use Disorder

Outcome Measures

Primary Outcomes (3)

• Assessment of Bioequivalence of Prototype Mini Lozenges With Nicorette Mini Lozenge by Measuring Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t (AUC [0-t])

  Bioequivalence of prototype mini lozenges with nicorette mini lozenge was assessed by measuring AUC(0-t), where t= time of the last measurable plasma concentration. AUC(0-t) was calculated using the linear trapezoidal with linear interpolation method. A linear mixed-effects model was fit to the natural log (ln)-transformed PK variable (AUC0-t), as the dependent variable, and treatment, period, and sequence as fixed effects. Participant nested within sequence was a random effect. The treatment difference and its 90% CI were exponentiated to obtain the geometric mean ratios (GMR) between the test and reference products and its 90% CI. Geometric Coefficient of variation was provided as percentage.

  0.75, 0.5, 0.25 hours predose and 0.08, 0.17, 0.33, 0.5, 0.67, 0.83, 1, 1.25, 1.5, 2, 3, 4, 6, 8 10, 14, 16, 20 and 24 hours postdose in each treatment period

• Assessment of Bioequivalence of Prototype Mini Lozenges With Nicorette Mini Lozenge by Measuring Area Under the Plasma Concentration Versus Time Curve Calculated From Time Zero to Infinity (AUC [(0-inf])

  Bioequivalence of prototype mini lozenges with nicorette mini lozenge was assessed by measuring AUC(0-inf). AUC(0-inf) = AUC0-t + (Clast/kel), where, AUC0-t= area under the plasma concentration versus time curve from time zero to time t; Clast= last observed/measured plasma concentration and kel= elimination rate constant. A linear mixed-effects model was fit to the natural log (ln)-transformed PK variable (AUC\[0-inf\]), as the dependent variable, and treatment, period, and sequence as fixed effects. Participant nested within sequence was a random effect. The treatment difference and its 90% CI were exponentiated to obtain the GMR between the test and reference products and its 90% CI. Geometric Coefficient of variation was provided as percentage.

  0.75, 0.5, 0.25 hours predose and 0.08, 0.17, 0.33, 0.5, 0.67, 0.83, 1, 1.25, 1.5, 2, 3, 4, 6, 8 10, 14, 16, 20 and 24 hours postdose in each treatment period

• Assessment of Bioequivalence of Prototype Mini Lozenges With Nicorette Mini Lozenge by Measuring Maximum Observed Plasma Nicotine Concentration (Cmax)

  Blood samples were collected at designated timepoints. Bioequivalence of prototype mini lozenges with nicorette mini lozenge was assessed by measuring Cmax that was taken directly from bioanalytical data. Geometric Coefficient of variation was provided as percentage. A linear mixed-effects model was fit to the natural log (ln)-transformed PK variable (Cmax) as the dependent variable, and treatment, period, and sequence as fixed effects. Participant nested within sequence was a random effect. The treatment difference and its 90% CI were exponentiated to obtain the GMR between the test and reference products and its 90% CI. Geometric Coefficient of variation was provided as percentage.

  0.75, 0.5, 0.25 hours predose and 0.08, 0.17, 0.33, 0.5, 0.67, 0.83, 1, 1.25, 1.5, 2, 3, 4, 6, 8 10, 14, 16, 20 and 24 hours postdose in each treatment period

Secondary Outcomes (4)

• Comparison of Prototype Mini Lozenges With Nicorette Mini Lozenge by Measuring Time of Maximum Plasma Nicotine Concentration (Tmax)

  0.75, 0.5, 0.25 hours predose and 0.08, 0.17, 0.33, 0.5, 0.67, 0.83, 1, 1.25, 1.5, 2, 3, 4, 6, 8 10, 14, 16, 20 and 24 hours postdose in each treatment period

• Comparison of Prototype Mini Lozenges With Nicorette Mini Lozenge by Measuring Apparent Elimination Half-Life (t1/2)

  0.75, 0.5, 0.25 hours predose and 0.08, 0.17, 0.33, 0.5, 0.67, 0.83, 1, 1.25, 1.5, 2, 3, 4, 6, 8 10, 14, 16, 20 and 24 hours postdose in each treatment period

• Comparison of Prototype Mini Lozenges With Nicorette Mini Lozenge by Measuring Apparent Elimination Rate Constant for Plasma Nicotine (Kel)

  0.75, 0.5, 0.25 hours predose and 0.08, 0.17, 0.33, 0.5, 0.67, 0.83, 1, 1.25, 1.5, 2, 3, 4, 6, 8 10, 14, 16, 20 and 24 hours postdose in each treatment period

• Number of Participants With Clinically Significant Change in Laboratory Test Values

  From signing of the informed consent form until 5 days after last administration of study drug (up to Day 13)

Study Arms (2)

Test Product

EXPERIMENTAL

Participants will receive a single Nicotine Prototype Mini lozenge (4mg) by oral/buccal route of administration.

Drug: Nicotine Prototype Mini lozenge

Reference Product

ACTIVE COMPARATOR

Participants will receive a single Nicorette Mini lozenge (4 mg) by oral/buccal route of administration.

Drug: Nicorette Mini Lozenge

Interventions

Nicotine Prototype Mini lozenge DRUG

A single dose of a prototype nicotine 4mg lozenge will be placed in participants mouth, occasionally moving it side to side. Allowing it to slowly dissolve and try to minimize swallowing. Participants will be instructed not to chew lozenge. The lozenge should be completely dissolved.

Test Product

Nicorette Mini Lozenge DRUG

A single dose of a 4 mg nicotine polacrilex mini lozenge (Nicorette Minis) will be placed in participants mouth, occasionally moving it side to side. Allowing it to slowly dissolve and try to minimize swallowing. Participants will be instructed not to chew lozenge. The lozenge should be completely dissolved.

Reference Product

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study before any assessment is performed.
• Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Healthy participants which is defined as in general good physical health, as judged by the investigator and no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure, respiratory rate, oral body temperature and pulse rate measurement, 12-lead ECG or clinical laboratory tests.
• Body Mass Index (BMI) of 19 to 27 Kilogram per meter square (kg/m2), inclusive; and a total body weight \>50 kg (110 pounds \[lbs\]).
• Female participants of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for at least 5 days after the last dose of assigned treatment. Female participants who are not of childbearing potential must meet at least one of the following criteria: a) Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state. b) Have undergone a documented hysterectomy and/or bilateral oophorectomy.
• Participant admits to having smoked commercially available cigarettes daily for the preceding 12 months and to routinely smoking his or her first cigarette within 30 minutes upon awakening. Brief periods of non-smoking (e.g. due to illness, trying to quit, participation in a study where smoking was prohibited) during that time will be permitted at the discretion of the PI (Principal Investigator).

You may not qualify if:

• Participants who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Participants who are GSK employees directly involved in the conduct of the study.
• Participation in other studies involving investigational drug(s) within 30 days prior to first dose and during study participation.
• 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 Participant inappropriate for entry into this study.
• Pregnant female Participants.
• Breastfeeding female Participants.
• Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients.
• Unwilling or unable to comply with the Lifestyle guidelines described in this protocol.
• Participant has used any nicotine replacement therapy within 21 days prior to the first study session.
• Participant has used chewing tobacco, tobacco products or electronic cigarettes other than cigarettes within 21 days of Visit 1.
• Use of prescription or non-prescription drugs and dietary supplements within two weeks or 5 half-lives, whichever is longer, prior to the first dose of investigational product until the end of the study. Allowed treatments are: Systemic contraceptives and hormone replacement therapy, as long as female Participant is on stable treatment for at least 3 months and continues treatment throughout the study. Evidence or history of clinically significant laboratory abnormality, hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease within the last 5 years that may increase the risk associated with study participation.
• History of regular alcohol consumption exceeding 14 drinks/week (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening.
• A positive urine drug screen for THC, amphetamine, cocaine, 3,4-methylenedioxy-N-methylamphetamine (MDMA)/ecstasy, methamphetamine, or opiates; and urine alcohol testing during screening or baseline testing.
• Participant is unwilling to abstain from tobacco or nicotine-containing product use during each study session (from start of baseline to the completion of the last PK blood sampling). CO measurement immediately prior to randomization (first treatment session) and dosing (second treatment session) should be ≤ 10 parts per million (ppm) for the Participant to be dosed.
• Participant ingests more than 5 cups of coffee or tea a day (or equivalent xanthine consumption using other products).
• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational product (whichever is longer).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Lincoln, Nebraska, 68502, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2018
• First Posted: June 1, 2018
• Study Start: June 18, 2018
• Primary Completion: November 12, 2018
• Study Completion: November 12, 2018
• Last Updated: December 4, 2019
• Results First Posted: December 4, 2019

Record last verified: 2019-11

Locations

US (1)