Phase 1 N=36 Randomized Treatment

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

Antifungal Agents

Bottom Line

View on ClinicalTrials.gov: NCT04318535 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Dec 2020

Primary outcome: Primary: Maximum Plasma Concentration (Cmax) for Griseofulvin — 2229; 2877; 1927 Nanograms per milliliter

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: Griseofulvin 500 mg (Drug); Griseofulvin 250 mg (Drug); Reference Griseofulvin 500 mg (Drug)
Age: Adult · 18+ yrs
Sex: All
Sponsor: GlaxoSmithKline
Primary completion: Jan 2020

Outcome Measures

Outcome	Result	p-value
PRIMARY Maximum Plasma Concentration (Cmax) for Griseofulvin	2229; 2877; 1927	—
PRIMARY Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Time of Last Quantifiable Concentration (AUC[0-t]) for Griseofulvin	54993; 66788; 53274	—
PRIMARY AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) for Griseofulvin	56746; 69564; 55100	—
PRIMARY Dose Proportionality of Griseofulvin Using AUC(0-t) Following a Single Dose	1.214	—
PRIMARY Dose Proportionality of Griseofulvin Using Cmax Following a Single Dose	1.290	—
SECONDARY Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (Non-SAE)	0; 0; 0; 0; 0; 1	—
SECONDARY Number of Participants With Any Abnormality in Vital Signs	0; 0; 0; 0; 0; 0	—
SECONDARY Number of Participants With Any Abnormality in Hematology Parameters	0; 0; 0; 0; 0; 0	—
SECONDARY Number of Participants With Any Abnormality in Clinical Chemistry Parameters	0; 0; 0; 0; 0; 0	—
SECONDARY Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT)	0; 0; 0; 0; 0; 0	—
SECONDARY Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants)	0; 0; 0; 0; 0; 0	—
SECONDARY Number of Participants With Abnormal Urinalysis Dipstick Results	0; 0; 0	—

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
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.
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 suppleme

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04318535). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.