Bioequivalence (BE) Study of Test Griseofulvin 500 Milligram (mg) Tablets Versus Reference and Dose Proportionality Study of Test Griseofulvin 250 mg and 500 mg Tablets Under Fed Conditions
Condition: Antifungal Agents
MeSH terms: Malnutrition
Intervention: Griseofulvin 500 mg; Griseofulvin 250 mg; Reference Griseofulvin 500 mg
Intervention description: Griseofulvin 500 mg will be administered as an oral tablet once in each treatment period under fed condition.; Griseofulvin 250 mg will be administered as an oral tablet once in each treatment period under fed condition.; Reference Griseofulvin 500 mg will be administered as an oral tablet once in each treatment period under fed condition.
Intervention MeSH terms: Griseofulvin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: The whole study will be divided into three treatment periods. For each treatment period, eligible participants will be randomized to either T1T2R, T2RT1 or RT1T2 treatment sequence according to 1:1:1 ratio
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Griseofulvin; Bioequivalence; Dose proportionality; Dermatophytosis

Summary:

      Griseofulvin is an antifungal agent used in treatment of Dermatophytosis caused by
      Microsporum spp. (species), Trichophyton spp., Epidermophyton spp., where topical therapy is
      considered inappropriate or has failed. Approved dose of Griseofulvin in Adults (greater than
      or equal to 50 kg) in India is 500 to 1,000 mg daily, but not less than 10 mg/kg bodyweight
      daily. As per the World health organization (WHO) guidance, Griseofulvin belongs to
      Biopharmaceutical Classification System (BCS) Class 2 ("low" solubility-"high" permeability).
      A Bioequivalence (BE) study will be conducted in India to estimate in vivo behavior
      (Pharmacokinetic characteristics) of Griseofulvin 500 tablets and dose proportionality study
      for Griseofulvin 250 mg and 500 mg tablets. This is an open label, randomized, balanced,
      three treatment period, three sequence, single dose, crossover study that will evaluate the
      bioequivalence of Griseofulvin tablets 500 mg test product (T1) versus Griseofulvin tablets
      500 mg reference product (R) as well as dose proportionality of Griseofulvin tablets 250 mg
      test product (T2) with Griseofulvin tablets 500 mg T1 in healthy, adult participants under
      fed conditions. Eligible participants enrolled will be randomized to either of the three
      treatment sequence periods, T1T2R, T2RT1 or RT1T2 according to 1:1:1 ratio. The total
      duration of clinical phase will be approximately 20 days from Day-1 to Day 19 including a
      washout period of at least 7 days (not more than 14 days) for each treatment period. A total
      of 36 healthy, adult participants will be enrolled in this study and the above mentioned
      doses of Griseofulvin will be administered under fed conditions. Participants will be
      followed up 5 days after last dosing.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant must be 18 to 45 years of age inclusive, at the time of signing the
             informed consent.

          -  Participants who are healthy as determined by the investigator or medically qualified
             designee on a medical evaluation including medical baseline history, physical
             examination and vital sign examination (blood pressure, pulse rate, respiration rate
             and body temperature).

          -  Participants with clinically acceptable findings as determined by hematology,
             biochemistry, urinalysis, 12 lead electrocardiogram (ECG).

          -  Participant's willingness to follow the protocol requirements especially abstaining
             from xanthine containing food or beverages (chocolates, tea, coffee or cola drinks) or
             grapefruit or grapefruit juice, any alcoholic products, the use of cigarettes and the
             use of tobacco products from 48 hours before the start of dosing until after
             collection of the final pharmacokinetic sample and adherence to food, fluid and
             posture restrictions.

          -  Participants with no history of significant alcoholism (Volunteers who do not have
             habit of heavy drinking which is defined as regular intake of more than 2 units of
             alcohol per day for male and 1 unit for female [I unit= 150 mL of wine or 360 mL of
             beer or 45 mL of 40 percent (%) of alcohol]).

          -  Participants with no history of drug abuse (benzodiazepines and barbiturates) for the
             last one month and other illegal drugs for the last 6 months.

          -  Participants who are non-smokers and ex-smokers will be included. "Ex-smokers are
             someone who completely stopped smoking for at least 3 months."

          -  Body mass index (BMI) within the range 18.5-30 kilogram per meter square (kg/m^2)
             (inclusive) and weight >= 50 kg.

          -  Healthy Male and non-pregnant female: Contraceptive use by men or women should be
             consistent with local regulations regarding the methods of contraception for those
             participating in clinical studies.

          -  Male participants are eligible to participate if they agree to the following during
             the treatment period and for at least six months after the last dose of study
             treatment.

             • Refrain from donating sperm as well as agree to use contraception/barrier as
             detailed below

               1. Agree to use a male condom and should also be advised for a female partner to use
                  a highly effective method of contraception as a condom may break or leak when
                  having sexual intercourse with a woman of childbearing potential who is not
                  currently pregnant.

               2. Agree to use male condom when engaging in any activity that allows for passage of
                  ejaculate to another person.

          -  A female participant is eligible to participate if she is not pregnant and intending
             to become pregnant or breastfeeding, and at least one of the following conditions
             applies:

               -  Is not a woman of childbearing potential (WOCBP) OR

               -  Is a WOCBP and using a contraceptive method that is highly effective, with a
                  failure rate of <1% during the treatment period and for at least 1 month after
                  the last dose of study treatment. The investigator should evaluate the
                  effectiveness of the contraceptive method in relationship to the first dose of
                  study treatment.

               -  A WOCBP must have a negative highly sensitive pregnancy test (serum as required
                  by local regulations) within 1 day before each dose of study treatment (The
                  participant must be excluded from participation if the serum pregnancy result is
                  positive).

                  b) Additional requirements for pregnancy testing during and after study
                  treatment.

                  c) The investigator is responsible for review of medical history, menstrual
                  history, and recent sexual activity to decrease the risk for inclusion of a woman
                  with an early undetected pregnancy.

          -  Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions listed in the informed consent form (ICF) and in this
             protocol.

        Exclusion Criteria:

          -  Known history of hypersensitivity to Griseofulvin.

          -  Participants who have taken prescription medications or over-the-counter products
             (including vitamins, minerals and/or herbal supplements) within 14 days prior to
             administration of Investigational Medicinal Product (IMP).

          -  Any medical or surgical conditions, which might significantly interfere with the
             functioning of gastrointestinal tract, blood-forming organs, etc.

          -  History of cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological,
             metabolic, hematological, gastrointestinal, endocrine, immunological or psychiatric
             diseases.

          -  History of malignancy (including skin cancers) or other serious diseases.

          -  History of porphyria.

          -  Known history of Systemic lupus erythematosus (SLE) in the exclusion criteria.

          -  Participants consuming aspirin, oral contraceptive pills, phenobarbital, and warfarin
             having potential to trigger drug interactions with Griseofulvin for any ailment in the
             previous 28 days, prior to dosing day.

          -  Participation in a clinical drug study or bioequivalence study 90 days prior to period
             I dosing of the present study.

          -  Participants with positive Human Immuno Deficiency Virus (HIV) tests, Hepatitis B
             Surface Antigen (HBsAg) or Hepatitis-C tests.

          -  Found positive in breath alcohol test.

          -  Found positive in urine test for drug abuse.

          -  Blood donation 90 days prior to period I dosing of the present study.

          -  History of problem in swallowing pills.

          -  Any contraindication to blood sampling i.e. keloid formation.

          -  Sensitivity to heparin or heparin-induced thrombocytopenia.

          -  Premenarchal female participants.