A Bioavailability Crossover Study of Two Formulations of Lamotrigine Extended Release Tablets in Healthy Subjects

NCT02821338 | Completed Phase 1 Results

• 1 other identifier: 15-099D
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to determine bioequivalence between two different formulations of lamotrigine extended release tablets (one reference product and one generic product) in a healthy adult population, following a single oral dose under fed conditions.

Conditions

Healthy

Keywords

Bioequivalence; Lamotrigine Extended Release; Generic; Pharmacokinetic

Outcome Measures

Primary Outcomes (3)

• Area Under the Lamotrigine Concentration vs. Time Curve From Sample Time Point 0 Hour to Sample Time Point 144 Hour.

  Pre-dose, and post-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36, 48, 72, 96, 120, 144 hours Lamotrigine and Lamictal have the same active ingredient "Lamotrigine."

  144 hours

• AUC 0-Inf

  Area Under the Lamotrigine Concentrations vs. time curve from sample time point 0 hour to sample time point 144hours plus extrapolation to infinity of the terminal concentration slope. This describes the total exposure to Lamotrigine. Sampling times include: Pre-dose, and post-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36, 48, 72, 96, 120, 144 hours. Lamotrigine and Lamictal have the same active ingredient.

  144 hours

• Cmax

  The maximum concentration of the Lamotrigine achieved in specified time frame for each treatment. Sampling times include: post-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36, 48, 72, 96, 120, 144 hours. Lamotrigine and Lamictal have the same active ingredient.

  2 to 144 hours

Other Outcomes (3)

• Tmax

  2 to 144 hours

• λZ

  2 to 144 hours

• Thalf

  2 to 144 hours

Study Arms (2)

Sequence 1

ACTIVE COMPARATOR

The treatments will be administered according to a randomly assigned pre-generated sequence involving the randomized, four-period, two sequence, fully replicate crossover design. Two study drugs involved are: Lamotrigine Extended Release (generic) and Lamictal XR (brand).

Drug: Lamotrigine Extended Release

Sequence 2

ACTIVE COMPARATOR

The treatments will be administered according to a randomly assigned pre-generated sequence involving the four-period, two sequence, fully replicate crossover design. Two study drugs involved are: Lamotrigine Extended Release (generic) and Lamictal XR (brand).

Drug: Lamotrigine Extended Release

Interventions

Lamotrigine Extended Release DRUG

Lamotrigine Extended Release (generic) and Lamictal XR (brand).

Also known as: Lamictal XR

Sequence 1; Sequence 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female subjects ≥18 to ≤50 years of age
• Subject is willing and able to provide informed consent
• Body mass index (BMI) greater than or equal to 18.00 kg/m2 and below 30.00 kg/m2 at screening
• Body weight greater than or equal to 50 kg at screening
• Subject is a non-smoker and has not used any nicotine containing products within 6 months prior to screening
• Subjects who are considered generally healthy upon completion of medical history, physical examination, vital signs, screening laboratory results and screening ECG in the opinion of the Investigator
• Subjects who are willing and able to comply with the visit schedule, laboratory tests, pharmacokinetic sampling schedule and other study procedures
• Subjects who are willing and able to maintain their eligibility throughout the study.
• A female study subject must meet one of the following criteria:
• If of childbearing potential - agrees to use one of the accepted contraceptive regimens from at least 30 days prior to the first administration of the study medication, during the study, and for at least 30 days after the last dose of the study medication. An acceptable method of contraception includes one of the following:
• Abstinence from heterosexual intercourse
• Progestogen-containing hormonal contraceptives (birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch)
• Intrauterine device (without hormones)
• Condom with spermicide
• If a female of non-childbearing potential - should be surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (at least 1 year without menses), as confirmed by FSH levels (post menopausal must be confirmed by the subject having a serum follicle stimulating hormone greater than 40mIU/ml at screening). Females of non-childbearing potential must present a proof of partial or total hysterectomy; if such proof is not available, the female will be considered to be of childbearing potential.

You may not qualify if:

• Females who are pregnant or are breastfeeding
• Females who are using any estrogen-containing hormonal contraceptives
• History of known clinically significant drug allergies or reactions to lamotrigine, or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs in the opinion of the Investigator
• Clinically significant history or evidence of gastrointestinal, hepatic, renal, endocrine, pulmonary, neurological, psychiatric, cardiovascular, hematologic, dermatologic, immunologic disease or any other condition known to interfere with the absorption, distribution, metabolism or distribution of drugs that in the opinion of the Investigator would jeopardize the safety of the subject or impact validity of study results
• Presence of observed abnormality (evidenced from physical examination, ECG, vital signs, or laboratory evaluation) that would be clinically significant in the opinion of the Investigator
• History of regular alcohol consumption exceeding 7 drinks per week for females and 14 drinks per week for males within 6 months of screening
• Has current or recent history (within the past year) of alcohol or drug abuse or dependence
• Any clinically significant illness in the previous 30 days prior to screening
• Use of any enzyme-modifying drugs, including strong inhibitors of CYP enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin, St John's Wort) in the previous 30 days prior to screening
• Known presence of rare hereditary problems of galactose and /or lactose intolerance or glucose-galactose malabsorption
• Unusual dietary habits (e.g., vegan, Atkins), dietary restrictions, and/or food allergies.
• Any planned surgery from the screening visit until the end of the study
• Positive urine screen for alcohol, cotinine and/or drugs of abuse at screening and at each admission of each treatment period
• Positive test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen (HBsAg) or Hepatitis C Antibody (HCVAb)
• Albumin values less than 4 g/dL at screening

Sponsors & Collaborators

• Food and Drug Administration (FDA): lead
• Vince & Associates Clinical Research, Inc.: collaborator
• Algorithme Pharma Inc: collaborator

Study Sites (1)

Vince and Associates Clinical Research, Inc

Overland Park, Kansas, 66212, United States

Location

Related Links

• Clinical site

Results Point of Contact

• Title: Office of Generic Drugs, Center for Drug Evaluation and Research
• Organization: US Food and Drug Administration

genericdrugs@fda.hhs.gov

240-402-7920

Study Officials

• Bradley Vince, D.O.

  Vince and Associates Clinical Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 29, 2016
• First Posted: July 1, 2016
• Study Start: June 1, 2016
• Primary Completion: September 1, 2016
• Study Completion: April 1, 2017
• Last Updated: May 1, 2020
• Results First Posted: May 1, 2020

Record last verified: 2020-04

Locations

US (1)