A Bioequivalence Study Between Two Nicotine Replacement Therapies in Adult Healthy Smokers Motivated to Quit.

NCT03130179 | Completed Phase 1

• 1 other identifier: CO-141210150531-SCCT
• Study Type: interventional
• Target: 244
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study to verify the same effectiveness and safety profile for the test product, Nicorette Strongmint lozenge, as for an already approved product, NiQuitin® Minimint lozenge (reference product), in a standardized mode. This verification is done in a so-called bioequivalence study, which means that the same amount of the same active substance (nicotine), in the same dosage form, for the same route of administration, and meeting the same or comparable standards is performed. During the study visits, blood samples will be drawn to measure the level of the substance in the blood to verify that the two products are comparable. Tolerability of the treatments will be evaluated based on reported and observed adverse events.

Conditions

Tobacco Dependence

Keywords

Bioequivalence

Outcome Measures

Primary Outcomes (7)

• Peak Plasma Concentration (Cmax) of nicotine

  The maximum observed plasma concentration (Cmax)

  At baseline, 10, 15, 20, 30, 40, 50 and 60 minutes, 1.25, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours after start of drug administration.

• The time at which the maximum nicotine concentration (Cmax) occurs (Tmax)

  Tmax is defined as the time point at which the maximum nicotine concentration (Cmax) occurs

  At baseline, 10, 15, 20, 30, 40, 50 and 60 minutes, 1.25, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours after start of drug administration.

• Area under the plasma concentration versus time curve (AUCt) from start of nicotine administration until the last measurable concentration.

  AUCt is defines as area under the plasma concentration versus time curves from start of drug administration until the last measureable concentration.

  At baseline, 10, 15, 20, 30, 40, 50 and 60 minutes, 1.25, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours after start of drug administration.

• Area under the plasma concentration versus time curve (AUC∞) of nicotine

  AUC∞ is defined as area under the plasma concentration versus time curves from start of drug administration until the nicotine plasma concentration is negligible (infinity).

  At baseline, 10, 15, 20, 30, 40, 50 and 60 minutes, 1.25, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours after start of drug administration.

• The extrapolated part of area under the plasma concentration versus time curve (AUC∞) of nicotine.

  The area under the plasma concentration versus time curves from start of drug administration until infinity.

  Extrapolation from 12 hours after start of drug administration until infinity.

• Determination of the terminal elimination rate constant (lambda_z) for nicotine.

  The rate at which the drug is removed from the body system.

  At baseline, 10, 15, 20, 30, 40, 50 and 60 minutes, 1.25, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours after start of drug administration.

• The plasma half-life (t1/2) of nicotine.

  The time taken for the nicotine plasma concentration to fall to half its original value.

  At baseline, 10, 15, 20, 30, 40, 50 and 60 minutes, 1.25, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours after start of drug administration.

Secondary Outcomes (6)

• Percentage of Subjects with Treatment-Emergent Adverse Events after single-dose administration of Nicorette Strongmint Lozenge 4mg or NiQuitin Minimint Lozenge 4mg.

  From first dose received up to 3.5 weeks + 30 days follow up after study completion for any unresolved adverse events.

• Percentage of Subjects with Treatment-Emergent Adverse Events after single-dose administration of Nicorette Strongmint Lozenge 4mg or NiQuitin Minimint Lozenge 4mg - By Worst-Case Severity.

  From first dose received up to 3.5 weeks + 30 days follow up after study completion for any unresolved adverse events.

• Percentage of Subjects with common treatment-emergent adverse events (AEs) after single-dose administration of Nicorette Strongmint Lozenge 4mg or NiQuitin Minimint Lozenge 4mg.

  From first dose received up to 3.5 weeks + 30 days follow up after study completion for any unresolved adverse events.

• Percentage of Subjects with treatment-related adverse events (AEs) after single-dose administration of Nicorette Strongmint Lozenge 4mg or NiQuitin Minimint Lozenge 4mg.

  From first dose received up to 3.5 weeks + 30 days follow up after study completion for any unresolved adverse events.

• Percentage of Subjects with treatment-related adverse events (AEs) after single-dose administration of Nicorette Strongmint Lozenge 4mg or NiQuitin Minimint Lozenge 4mg - By Worst-Case Severity.

  From first dose received up to 3.5 weeks + 30 days follow up after study completion for any unresolved adverse events.

Study Arms (2)

Nicorette Strongmint lozenge 4mg

EXPERIMENTAL

A single dose of one nicotine 4 mg lozenge will be administrated orally to slowly dissolve in the mouth for nicotine absorption via the buccal mucosa.

Drug: Nicorette Strongmint lozenge 4 mg

Niquitin Minimint lozenge 4mg

ACTIVE COMPARATOR

A single dose of one nicotine 4mg lozenge will be administrated orally to slowly dissolve in the mouth for nicotine absorption via the buccal mucosa.

Drug: Niquitin MiniMint lozenge 4 mg

Interventions

Nicorette Strongmint lozenge 4 mg DRUG

A single dose of one Nicorette lozenge 4mg lozenge administrated orally to slowly dissolve in the mouth.

Also known as: Nicorette lozenge 4 mg

Nicorette Strongmint lozenge 4mg

Niquitin MiniMint lozenge 4 mg DRUG

A single dose of one Niquitin Minimint lozenge 4mg administrated orally to slowly dissolve in the mouth.

Also known as: Niquitin lozenge 4 mg

Niquitin Minimint lozenge 4mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and/or female subjects 18 to 45 years of age, inclusive, and being verified "Healthy". ("Healthy" is defined as absence of any diseases or abnormalities on the basis of physical examination, standard clinical laboratory and instrumental examinations performed at the screening visit).
• Subjects with a Body Mass Index (BMI) between 18.5 to 30 kg/m2, inclusive, and a body weight \>50 kg.
• Females of childbearing potential must have a negative urine pregnancy test at the screening visit.
• Male or non-pregnant, non-lactating female agree to the contraceptive requirements (including male's and female partner's use of a highly effective methods of birth control for at least 3 months before the study, during the study and for 30 days after the last dose of study drug) as outlined in Section 10.7
• Has a personally signed and dated informed consent document before participating in any study-specific procedures, indicating that the subject has been informed of all pertinent aspects of the study; and
• Is able to comprehend the requirements of the study (based upon clinical site personnel's assessment), and is willing and able to comply with scheduled visits,treatment plan, laboratory tests, and other study procedures specified in the protocol.

You may not qualify if:

• Deviations from normal ranges as a result of standard clinical laboratory and instrumental examinations including ECG, performed at the screening visit.
• Use of vitamins, herbal supplements and medicinal plants (e.g. garlic) within 7 days before the first dose of study medication. Use of products containing St. John's wort \[Hypericum perforatum\] 30 days prior to the study start.
• Intake of medications having a significant impact on hemodynamics, hepatic function etc. (e.g. \[but not limited to\] barbiturates, omeprazole cimetidine).
• Subjects who will not abstain from using nicotine-containing products (besides treatments specified in this protocol) and smoking from 12 hours before planned treatment intake and throughout each visit.
• Is hypersensitive, intolerant, or experienced an allergic reaction to the active ingredient(s) or excipients of drug products that will be used in the study or has severe allergy (e.g. anaphylaxis, angioedema) in the past.
• Females with a positive pregnancy test and/or are breast-feeding.
• Females, currently using hormonal contraceptives, (including use less than 2 weeks prior to enrollment)
• Males with a pregnant spouse or partner or males who are not willing to prevent conception in a spouse or partner.
• Has a positive test for human immunodeficiency virus (HIV) 1 and 2 antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (anti-HCV) or syphilis (RW).
• Has a positive test for psychoactive and narcotic substances, psychoactive drugs at screening and/or at any admission to the clinical center or has drugs abuse in the past.
• Consumes alcohol regularly in excess of the following: \>10 units per week (1 unit of alcohol is equivalent to ½ liter of beer, 200 ml wine or 50 ml of vodka) or presence of information on alcoholism in medical history. The subject must also abstain from alcohol consumption within 48 hours prior to the screening visit and have a negative respiratory alcohol test at the screening visit and/or at any admission clinical center (breathalyzer).
• Use of xanthine products within 48 hours prior to the first dose of the investigational product.
• Ingestion of food or beverages containing grapefruit, Chinese grapefruit (pomelo) or Seville oranges (including marmalade) within 10 days prior to the first dose of the investigational product and inability to stop these products taking during the study.
• Abuse of caffeine products exceeding 500mg caffeine daily (5 cups of coffee) and the ability to abstain from caffeine products at least 48 hours before the first dose of investigational product intake and prior to prior to collection of the last blood sample in each period of the study.
• Renal or hepatic impairment.

Sponsors & Collaborators

• McNeil AB: lead

Study Sites (1)

"Scientific and Clinical Center of JSC "RZD"

Moscow, Russia

Location

Related Links

• CSR Synopsis

MeSH Terms

Conditions

Tobacco Use Disorder

Condition Hierarchy (Ancestors)

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

Study Officials

• Elena P Mazygula, MD

  "Scientific and Clinical Center of JSC "RZD"

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 29, 2017
• First Posted: April 26, 2017
• Study Start: March 20, 2017
• Primary Completion: June 19, 2017
• Study Completion: June 29, 2017
• Last Updated: July 27, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)